Skip to main content

Advertisement

SpringerLink
Log in

Key promoters of tumor hallmarks

  • Review Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Evolution of tumor hallmarks is a result of accommodation of tumor cells with their nearby milieu called tumor microenvironment (TME). Accommodation or adaptive responses is highly important for a cell to survive, without which no cell is allowed to take any further steps in tumorigenesis. Metabolism of cancer cells is largely depended on stroma. Composition and plasticity of cells within the stroma is highly affected from inflammatory setting of TME. Hypoxia which is a common event in many solid cancers, is known as one of the key hallmarks of chronic inflammation and the master regulator of metastasis. Transforming growth factor (TGF)-β is produced in the chronic inflammatory and chronic hypoxic settings, and it is considered as a cardinal factor for induction of all tumor hallmarks. Aging, obesity and smoking are the main predisposing factors of cancer, acting mainly through modulation of TME.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of data and materials

Not applicable.

References

  1. Goradel NH, Mohajel N, Malekshahi ZV et al (2019) Oncolytic adenovirus: a tool for cancer therapy in combination with other therapeutic approaches. J Cell Physiol 234(6):8636–8646

    Article  CAS  PubMed  Google Scholar 

  2. Najafi M, Majidpoor J, Toolee H et al (2021) The current knowledge concerning solid cancer and therapy. J Biochem Mol Toxicol 2021:e22900

    Google Scholar 

  3. Najafi M, Shayesteh MRH, Mortezaee K et al (2020) The role of melatonin on doxorubicin-induced cardiotoxicity: a systematic review. Life Sci 241:117173

    Article  CAS  PubMed  Google Scholar 

  4. Lee SY, Jeong EK, Ju MK et al (2017) Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol Cancer 16(1):10

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rolny C, Mazzone M, Tugues S et al (2011) HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell 19(1):31–44

    Article  CAS  PubMed  Google Scholar 

  6. Zhu J, Thompson CB (2019) Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol 20(7):436–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang X, Luo G, Zhang K et al (2018) Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Can Res 78(16):4586–4598

    Article  CAS  Google Scholar 

  8. Thienpont B, Steinbacher J, Zhao H et al (2016) Tumour hypoxia causes DNA hypermethylation by reducing TET activity. Nature 537(7618):63–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Angeli JPF, Krysko DV, Conrad M (2019) Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer 19(7):405–414

    Article  Google Scholar 

  10. Garner H, de Visser KE (2020) Immune crosstalk in cancer progression and metastatic spread: a complex conversation. Nature Rev Immunol 2020:1–15

    Google Scholar 

  11. Mollinedo F (2019) Neutrophil degranulation, plasticity, and cancer metastasis. Trends Immunol 40:228–242

    Article  CAS  PubMed  Google Scholar 

  12. Öhlund D, Elyada E, Tuveson D (2014) Fibroblast heterogeneity in the cancer wound. J Exp Med 211(8):1503–1523

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mantovani A, Dinarello CA, Molgora M et al (2019) Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity 50(4):778–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mehrian-Shai R, Reichardt JK, Harris CC et al (2019) The gut–brain axis, paving the way to brain cancer. Trends Cancer. 5:200–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Greten FR, Grivennikov SI (2019) Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 51(1):27–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mortezaee K, Najafi M, Farhood B et al (2020) Resveratrol as an adjuvant for normal tissues protection and tumor sensitization. Curr Cancer Drug Targets 20(2):130–145

    Article  CAS  PubMed  Google Scholar 

  17. Bose M, Mukherjee P (2019) Microbe–MUC1 crosstalk in cancer-associated infections. Trends Mol Med 3:324–336

    Google Scholar 

  18. Hinohara K, Polyak K (2019) Intratumoral heterogeneity: more than just mutations. Trends Cell Biol 29:569–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Williams CB, Yeh ES, Soloff AC (2016) Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy. NPJ Breast Cancer 2(1):1–12

    Article  Google Scholar 

  20. Altorki NK, Markowitz GJ, Gao D et al (2019) The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer 19(1):9–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hashemi Goradel N, Heidarzadeh S, Jahangiri S et al (2019) Fusobacterium nucleatum and colorectal cancer: a mechanistic overview. J Cell Physiol 234(3):2337–2344

    Article  CAS  PubMed  Google Scholar 

  22. Shacter E, Weitzman SA (2002) Chronic inflammation and cancer. J Cell Physiol 234:2337–2344

    Google Scholar 

  23. Fluckiger A, Dumont A, Derangere V et al (2016) Inhibition of colon cancer growth by docosahexaenoic acid involves autocrine production of TNFα. Oncogene 35(35):4611–4622

    Article  CAS  PubMed  Google Scholar 

  24. Li W, Zhang X, Chen Y et al (2016) G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers. Protein Cell 7(2):130–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lau EYT, Lo J, Cheng BYL et al (2016) Cancer-associated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular carcinoma through c-Met/FRA1/HEY1 signaling. Cell Rep 15(6):1175–1189

    Article  CAS  PubMed  Google Scholar 

  26. Craig AJ, von Felden J, Garcia-Lezana T et al (2019) Tumour evolution in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2019:1–14

    Google Scholar 

  27. Mortezaee K, Sabbaghziarani F, Omidi A et al (2016) Therapeutic value of melatonin post-treatment on CCl4-induced fibrotic rat liver. Can J Physiol Pharmacol 94(2):119–130

    Article  CAS  PubMed  Google Scholar 

  28. Mortezaee K, Majidpoor J, Daneshi E et al (2018) Post-treatment of melatonin with CCl4 better reduces fibrogenic and oxidative changes in liver than melatonin co-treatment. J Cell Biochem 119(2):1716–1725

    Article  CAS  PubMed  Google Scholar 

  29. El-Kenawi A (2019) When T cells lap up lactate. Sci Transl Med. 11(519). https://doi.org/10.1126/scitranslmed.aaz9753

  30. D’Amico E, Chisari CG, Arena S et al (2019) Cancer risk and multiple sclerosis: evidence from a large Italian Cohort. Front Neurol 10:337. https://doi.org/10.3389/fneur.2019.00337

  31. Hermann PC, Sainz Jr B (2018) Pancreatic cancer stem cells: a state or an entity? Elsevier, pp 223–231

  32. Burn J, Sheth H, Elliott F et al (2020) Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet 395(10240):1855–1863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nakamura K, Smyth MJ (2017) Targeting cancer-related inflammation in the era of immunotherapy. Immunol Cell Biol 95(4):325–332

    Article  CAS  PubMed  Google Scholar 

  34. Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8(8):604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Albini A, Tosetti F, Li VW et al (2012) Cancer prevention by targeting angiogenesis. Nat Rev Clin Oncol 9(9):498

    Article  CAS  PubMed  Google Scholar 

  36. Galon J, Bruni D (2020) Tumor immunology and tumor evolution: intertwined histories. Immunity 52(1):55–81

    Article  CAS  PubMed  Google Scholar 

  37. Mortezaee K (2021) Organ tropism in solid tumor metastasis: an updated review. Future Oncol 17:1943–1961

    Article  CAS  PubMed  Google Scholar 

  38. Najafi M, Mortezaee K, Majidpoor J (2019) Stromal reprogramming: a target for tumor therapy. Life Sci 239:117049

    Article  CAS  PubMed  Google Scholar 

  39. De Jaeghere EA, Denys HG, De Wever O (2019) Fibroblasts fuel immune escape in the tumor microenvironment. Trends Cancer 5:704–723

    Article  PubMed  Google Scholar 

  40. Nakamura K, Smyth MJ (2019) Myeloid immunosuppression and immune checkpoints in the tumor microenvironment. Cell Mol Immunol 17:1–12

    Article  PubMed  PubMed Central  Google Scholar 

  41. Mortezaee K (2021) Myeloid-derived suppressor cells in cancer immunotherapy-clinical perspectives. Life Sci 277:119627

    Article  CAS  PubMed  Google Scholar 

  42. Kozlova N, Grossman JE, Iwanicki MP et al (2020) The interplay of the extracellular matrix and stromal cells as a drug target in stroma-rich cancers. Trends Pharmacol Sci 41:183–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gadalla R, Hassan H, Ibrahim SA et al (2019) Tumor microenvironmental plasmacytoid dendritic cells contribute to breast cancer lymph node metastasis via CXCR4/SDF-1 axis. Breast Cancer Res Treat 174(3):679–691

    Article  CAS  PubMed  Google Scholar 

  44. Mortezaee K, Goradel NH, Amini P et al (2019) NADPH oxidase as a target for modulation of radiation response; implications to carcinogenesis and radiotherapy. Curr Mol Pharmacol 12(1):50–60

    Article  CAS  PubMed  Google Scholar 

  45. Dai W, Wu J, Wang D et al (2020) Cancer gene therapy by NF-κB-activated cancer cell-specific expression of CRISPR/Cas9 targeting telomeres. Gene Ther 1056:1–15

    Google Scholar 

  46. Rodriguez-Ruiz ME, Vitale I, Harrington KJ et al (2019) Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. Nat Immunol 21:1–15

    Google Scholar 

  47. Di Conza G, Tsai C-H, Ho P-C (2019) Fifty shades of α-Ketoglutarate on cellular programming. Mol Cell 76(1):1–3

    Article  PubMed  Google Scholar 

  48. Pereira BA, Vennin C, Papanicolaou M et al (2019) CAF subpopulations: a new reservoir of stromal targets in pancreatic cancer. Trends Cancer 5:724–741

    Article  PubMed  Google Scholar 

  49. Mennerich D, Kubaichuk K, Kietzmann T (2019) DUBs, hypoxia, and cancer. Trends Cancer 5:632–653

    Article  CAS  PubMed  Google Scholar 

  50. McGuirk S, Audet-Delage Y, St-Pierre J (2020) Metabolic fitness and plasticity in cancer progression. Trends Cancer 6:49–61

    Article  CAS  PubMed  Google Scholar 

  51. Baik AH, Jain IH (2020) Turning the oxygen dial: balancing the highs and lows. Trends Cell Biol 30:516–536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Smith EA, Hodges HC (2019) The spatial and genomic hierarchy of tumor ecosystems revealed by single-cell technologies. Trends Cancer 5:411–425

    Article  PubMed  PubMed Central  Google Scholar 

  53. Zhang Q, Yan Q, Yang H et al (2019) Oxygen sensing and adaptability won the 2019 Nobel Prize in physiology or medicine. Genes Dis 6(4):328–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Farhood B, Najafi M, Mortezaee K (2019) Cancer-associated fibroblasts: secretions, interactions, and therapy. J Cell Biochem 120(3):2791–2800

    Article  CAS  PubMed  Google Scholar 

  55. Ye Y, Hu Q, Chen H et al (2019) Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy. Nat Metab 1(4):431–444

    Article  PubMed  PubMed Central  Google Scholar 

  56. Fares J, Fares MY, Khachfe HH et al (2020) Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther 5(1):1–17

    Google Scholar 

  57. Schito L, Semenza GL (2016) Hypoxia-inducible factors: master regulators of cancer progression. Trends Cancer 2(12):758–770

    Article  PubMed  Google Scholar 

  58. Semenza GL (2012) Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci 33(4):207–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Morandi A, Giannoni E, Chiarugi P (2016) Nutrient exploitation within the tumor–stroma metabolic crosstalk. Trends Cancer 2(12):736–746

    Article  PubMed  Google Scholar 

  60. Becker LM, O’Connell JT, Vo AP et al (2020) Epigenetic reprogramming of cancer-associated fibroblasts deregulates glucose metabolism and facilitates progression of breast cancer. Cell Rep 31(9):107701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Mortezaee K, Parwaie W, Motevaseli E et al (2019) Targets for improving tumor response to radiotherapy. Int Immunopharmacol 76:105847

    Article  CAS  PubMed  Google Scholar 

  62. Majidpoor J, Mortezaee K (2021) The efficacy of PD-1/PD-L1 blockade in cold cancers and future perspectives. Clin Immunol 226:108707

    Article  CAS  PubMed  Google Scholar 

  63. Mortezaee K (2021) Redox tolerance and metabolic reprogramming in solid tumors. Cell Biol Int 45(2):273–286

    Article  CAS  PubMed  Google Scholar 

  64. Farhood B, Najafi M, Salehi E et al (2019) Disruption of the redox balance with either oxidative or anti-oxidative overloading as a promising target for cancer therapy. J Cell Biochem 120(1):71–76

    Article  CAS  PubMed  Google Scholar 

  65. Mortezaee K (2020) Immune escape: a critical hallmark in solid tumors. Life Sci 258:118110

    Article  CAS  PubMed  Google Scholar 

  66. Adem B, Vieira PF, Melo SA (2019) Decoding the biology of exosomes in metastasis. Trends Cancer. 6:20–30

    Article  PubMed  Google Scholar 

  67. Mazzone M, Dettori D, Oliveira RL (2009) Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 136(5):839–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Majidpoor J, Mortezaee K (2021) Angiogenesis as a hallmark of solid tumors-clinical perspectives. Cell Oncol 44:715–737

    Article  CAS  Google Scholar 

  69. Batlle R, Andrés E, Gonzalez L et al (2019) Regulation of tumor angiogenesis and mesenchymal–endothelial transition by p38α through TGF-β and JNK signaling. Nat Commun 10(1):1–18

    Article  CAS  Google Scholar 

  70. Penticuff JC, Woolbright BL, Sielecki TM et al (2019) MIF family proteins in genitourinary cancer: tumorigenic roles and therapeutic potential. Nat Rev Urol 16(5):318–328

    Article  PubMed  Google Scholar 

  71. Jain I, Aguirre-Ghiso J, Jakob U et al (2020) Oxygen sensing: after the nobel. Cell Press 50 hampshire st, floor 5, Cambridge, MA 02139 USA

  72. Mortezaee K (2020) Hypoxia induces core-to-edge transition of progressive tumoral cells: a critical review on differential yet corroborative roles for HIF-1α and HIF-2α. Life Sci 242:117145

    Article  CAS  PubMed  Google Scholar 

  73. Nishide S, Matsunaga S, Shiota M et al (2019) Controlling the phenotype of tumor-infiltrating macrophages via the PHD-HIF axis inhibits tumor growth in a mouse model. iScience 19:940–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Mortezaee K (2021) Normalization in tumor ecosystem: opportunities and challenges. Cell Biol Int 45(10):2017–2030

  75. Majidpoor J, Mortezaee K (2021) Interleukin-2 therapy of cancer-clinical perspectives. Int Immunopharmacol 98:107836

    Article  CAS  PubMed  Google Scholar 

  76. Bosco MC, D’Orazi G, Del Bufalo D (2020) Targeting hypoxia in tumor: a new promising therapeutic strategy. J Exp Clin Cancer Res 39(1):1–3

    Google Scholar 

  77. Zy F, Zhang M, Liu J-N et al (2021) Tanshinone IIA: a review of its anticancer effects. Front Pharmacol 11:2189

    Google Scholar 

  78. Zhou L, Sui H, Wang T et al (2020) Tanshinone IIA reduces secretion of pro-angiogenic factors and inhibits angiogenesis in human colorectal cancer. Oncol Rep 43(4):1159–1168

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Scharping NE, Menk AV, Whetstone RD et al (2017) Efficacy of PD-1 blockade is potentiated by metformin-induced reduction of tumor hypoxia. Cancer Immunol Res 5(1):9–16

    Article  CAS  PubMed  Google Scholar 

  80. Incio J, Tam J, Rahbari NN et al (2016) PlGF/VEGFR-1 signaling promotes macrophage polarization and accelerated tumor progression in obesity. Clin Cancer Res 22(12):2993–3004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Mortezaee K, Shabeeb D, Musa AE et al (2019) Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization. Curr Clin Pharmacol 14(1):41–53

    Article  CAS  PubMed  Google Scholar 

  82. Gurrapu S, Tamagnone L (2019) Semaphorins as regulators of phenotypic plasticity and functional reprogramming of cancer cells. Trends Mol Med 25:303–314

    Article  CAS  PubMed  Google Scholar 

  83. Reina-Campos M, Linares JF, Duran A et al (2019) Increased serine and one-carbon pathway metabolism by PKCl/i deficiency promotes neuroendocrine prostate cancer. Cancer Cell 35:1–16

    Article  Google Scholar 

  84. Laudato S, Aparicio A, Giancotti FG (2019) Clonal evolution and epithelial plasticity in the emergence of ar-independent prostate carcinoma. Trends Cancer 5:440–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. García-Jiménez C, Goding CR (2019) Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming. Cell Metab 29(2):254–267

    Article  PubMed  Google Scholar 

  86. Phan TG, Croucher PI (2020) The dormant cancer cell life cycle. Nat Rev Cancer 20:1–14

    Article  Google Scholar 

  87. Boire A, Coffelt SB, Quezada SA et al (2019) Tumour dormancy and reawakening: opportunities and challenges. Trends Cancer 5(12):762–765

    Article  PubMed  Google Scholar 

  88. Romero-Moreno R, Curtis KJ, Coughlin TR et al (2019) The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis. Nat Commun 10(1):1–14

    Article  CAS  Google Scholar 

  89. Anderson RL, Balasas T, Callaghan J et al (2019) A framework for the development of effective anti-metastatic agents. Nat Rev Clin Oncol 16(3):185–204

    Article  PubMed  Google Scholar 

  90. Matzner P, Sandbank E, Neeman E et al (2020) Harnessing cancer immunotherapy during the unexploited immediate perioperative period. Nat Rev Clin Oncol 17:313–326

    Article  PubMed  Google Scholar 

  91. Williams ED, Gao D, Redfern A et al (2019) Controversies around epithelial–mesenchymal plasticity in cancer metastasis. Nat Rev Cancer 19:716–732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Majidpoor J, Mortezaee K (2021) Steps in metastasis: an updated review. Med Oncol 38(1):1–17

    Article  Google Scholar 

  93. Su W, Han HH, Wang Y et al (2019) The polycomb repressor complex 1 drives double-negative prostate cancer metastasis by coordinating stemness and immune suppression. Cancer Cell 36(2):139-155.e10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Pastushenko I, Blanpain C (2019) EMT transition states during tumor progression and metastasis. Trends Cell Biol 29(3):212–226

    Article  CAS  PubMed  Google Scholar 

  95. Cooper J, Giancotti FG (2019) Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell 35(3):347–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Diepenbruck M, Christofori G (2016) Epithelial–mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr Opin Cell Biol 43:7–13

    Article  CAS  PubMed  Google Scholar 

  97. Gorgoulis V, Adams PD, Alimonti A et al (2019) Cellular senescence: defining a path forward. Cell 179(4):813–827

    Article  CAS  PubMed  Google Scholar 

  98. Perez-Mancera PA, Young AR, Narita M (2014) Inside and out: the activities of senescence in cancer. Nat Rev Cancer 14(8):547–558

    Article  CAS  PubMed  Google Scholar 

  99. Nardella C, Clohessy JG, Alimonti A et al (2011) Pro-senescence therapy for cancer treatment. Nat Rev Cancer 11(7):503–511

    Article  CAS  PubMed  Google Scholar 

  100. Zhao Y, Shao Q, Peng G (2019) Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment. Cell Mol Immunol 17:27–35

    Article  PubMed  PubMed Central  Google Scholar 

  101. Faget DV, Ren Q, Stewart SA (2019) Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer 19(8):439–453

    Article  CAS  PubMed  Google Scholar 

  102. Faheem MM, Seligson ND, Ahmad SM et al (2020) Convergence of therapy-induced senescence (TIS) and EMT in multistep carcinogenesis: current opinions and emerging perspectives. Cell Death Discov 6(1):1–12

    Article  Google Scholar 

  103. Kim YH, Choi YW, Lee J et al (2017) Senescent tumor cells lead the collective invasion in thyroid cancer. Nat Commun 8(1):1–14

    Google Scholar 

  104. Fane M, Weeraratna AT (2019) How the ageing microenvironment influences tumour progression. Nat Rev Cancer 20:1–18

    Google Scholar 

  105. Ji Y, Fioravanti J, Zhu W et al (2019) miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate. Nat Commun 10(1):1–12

    Article  Google Scholar 

  106. Liu X, Mo W, Ye J et al (2018) Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition. Nat Commun 9(1):1–16

    Google Scholar 

  107. Costa TD, Zhuang T, Lorent J et al (2019) PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer. Nat Commun 10(1):1–18

    Article  Google Scholar 

  108. Wolter K, Zender L (2020) Therapy-induced senescence—an induced synthetic lethality in liver cancer? Nat Rev Gastroenterol Hepatol 17:1–2

    Article  Google Scholar 

  109. Kurppa KJ, Liu Y, To C et al (2020) Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway. Cancer Cell 37(1):104–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Valkenburg KC, de Groot AE, Pienta KJ (2018) Targeting the tumour stroma to improve cancer therapy. Nat Rev Clin Oncol 15(6):366–381

    Article  PubMed  PubMed Central  Google Scholar 

  111. Kobayashi H, Enomoto A, Woods SL et al (2019) Cancer-associated fibroblasts in gastrointestinal cancer. Nat Rev Gastroenterol Hepatol 16(5):282–295

    Article  PubMed  Google Scholar 

  112. Pelon F, Bourachot B, Kieffer Y et al (2020) Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat Commun 11(1):1–20

    Article  Google Scholar 

  113. Kalluri R (2016) The biology and function of fibroblasts in cancer. Nat Rev Cancer 16(9):582

    Article  CAS  PubMed  Google Scholar 

  114. Ji Q, Zhou L, Sui H et al (2020) Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation. Nat Commun 11(1):1–18

    Article  CAS  Google Scholar 

  115. Pein M, Insua-Rodríguez J, Hongu T et al (2020) Metastasis-initiating cells induce and exploit a fibroblast niche to fuel malignant colonization of the lungs. Nat Commun 11(1):1–18

    Article  Google Scholar 

  116. Salmon H, Remark R, Gnjatic S et al (2019) Host tissue determinants of tumour immunity. Nat Rev Cancer 19(4):215–227

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Ligorio M, Sil S, Malagon-Lopez J et al (2019) Stromal microenvironment shapes the intratumoral architecture of pancreatic cancer. Cell 178(1):160–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Coller HA (2019) Fibroblasts prompt tumors to mobilize their glycogen reserves. Trends Cell Biol 29(4):278–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Hanley CJ, Thomas GJ (2021) Targeting cancer associated fibroblasts to enhance immunotherapy: emerging strategies and future perspectives. Oncotarget 12(14):1427

    Article  PubMed  PubMed Central  Google Scholar 

  120. Sharbeen G, McCarroll JA, Akerman A et al (2021) Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma determine response to SLC7A11 inhibition. Cancer Res 5:141

    Google Scholar 

  121. Yi X, Yan Y, Li L et al (2021) Sequentially targeting cancer-associated fibroblast and mitochondria alleviates tumor hypoxia and inhibits cancer metastasis by preventing “soil” formation and “seed” dissemination. Adv Func Mater 31(17):2010283

    Article  CAS  Google Scholar 

  122. Sahai E, Astsaturov I, Cukierman E et al (2020) A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer 20(3):174–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Hawinkels LJ, Ten Dijke P (2011) Exploring anti-TGF-β therapies in cancer and fibrosis. Growth Factors 29(4):140–152

    Article  CAS  PubMed  Google Scholar 

  124. Batlle E, Massagué J (2019) Transforming growth factor-β signaling in immunity and cancer. Immunity 50(4):924–940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Derynck R, Turley SJ, Akhurst RJ (2020) TGFβ biology in cancer progression and immunotherapy. Nat Rev Clin Oncol 18:9–34

    Article  PubMed  Google Scholar 

  126. Mortezaee K (2021) Enriched cancer stem cells, dense stroma, and cold immunity: interrelated events in pancreatic cancer. J Biochem Mol Toxicol 35:e22708

    Article  CAS  PubMed  Google Scholar 

  127. Shalapour S, Karin M (2019) Pas de Deux: control of anti-tumor immunity by cancer-associated inflammation. Immunity 51(1):15–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Mortezaee K (2018) Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: a review. Cell Biochem Funct 36(6):292–302

    Article  CAS  PubMed  Google Scholar 

  129. Nolte M, Margadant C (2019) Controlling immunity and inflammation through integrin-dependent regulation of TGF-β. Trends Cell Biol 30:833

    Article  Google Scholar 

  130. Zhang W, Bado I, Wang H et al (2019) Bone metastasis: find your niche and fit in. Trends Cancer 5(2):95–110

    Article  PubMed  PubMed Central  Google Scholar 

  131. Chen J, Gingold JA, Su X (2019) Immunomodulatory TGF-β signaling in hepatocellular carcinoma. Trends Mol Med 25:1010–1023

    Article  CAS  PubMed  Google Scholar 

  132. Horton BL, Fessenden TB, Spranger S (2019) Tissue site and the cancer immunity cycle. Trends Cancer. 5:593–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Jackstadt R, van Hooff SR, Leach JD et al (2019) Epithelial NOTCH signaling rewires the tumor microenvironment of colorectal cancer to drive poor-prognosis subtypes and metastasis. Cancer Cell 36(3):319–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Shaul ME, Fridlender ZG (2019) Tumour-associated neutrophils in patients with cancer. Nat Rev Clin Oncol 16(10):601–620

    Article  PubMed  Google Scholar 

  135. Silvestre-Roig C, Fridlender ZG, Glogauer M et al (2019) Neutrophil diversity in health and disease. Trends Immunol 40:565–583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Biswas SK (2015) Metabolic reprogramming of immune cells in cancer progression. Immunity 43(3):435–449

    Article  CAS  PubMed  Google Scholar 

  137. Janiszewska M, Tabassum DP, Castaño Z et al (2019) Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nat Cell Biol 21(7):879–888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Liu S, Ren J, Ten Dijke P (2021) Targeting TGFβ signal transduction for cancer therapy. Signal Transduct Target Ther 6(1):1–20

    Google Scholar 

  139. Kim B-G, Malek E, Choi SH et al (2021) Novel therapies emerging in oncology to target the TGF-β pathway. J Hematol Oncol 14(1):1–20

    Article  Google Scholar 

  140. Faivre S, Santoro A, Kelley RK et al (2019) Novel transforming growth factor beta receptor I kinase inhibitor galunisertib (LY2157299) in advanced hepatocellular carcinoma. Liver Int 39(8):1468–1477

    Article  CAS  PubMed  Google Scholar 

  141. Kelley R, Gane E, Assenat E et al (2019) A phase 2 study of galunisertib (TGF-β1 receptor type I inhibitor) and sorafenib in patients with advanced hepatocellular carcinoma. Clin Transl Gastroenterol 10(7):e00056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Melisi D, Garcia-Carbonero R, Macarulla T et al (2019) TGFβ receptor inhibitor galunisertib is linked to inflammation-and remodeling-related proteins in patients with pancreatic cancer. Cancer Chemother Pharmacol 83(5):975–991

    Article  CAS  PubMed  Google Scholar 

  143. Melisi D, Garcia-Carbonero R, Macarulla T et al (2018) Galunisertib plus gemcitabine vs gemcitabine for first-line treatment of patients with unresectable pancreatic cancer. Br J Cancer 119(10):1208–1214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Christenson ES, Jaffee E, Azad NS (2020) Current and emerging therapies for patients with advanced pancreatic ductal adenocarcinoma: a bright future. Lancet Oncol 21(3):e135–e145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Lind H, Gameiro SR, Jochems C et al (2020) Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances. J Immunother Cancer 8(1):e000433

    Article  PubMed  PubMed Central  Google Scholar 

  146. Shi X, Young CD, Zhou H et al (2020) Transforming growth factor-β signaling in fibrotic diseases and cancer-associated fibroblasts. Biomolecules 10(12):1666

    Article  CAS  PubMed Central  Google Scholar 

  147. Zaitsu M, Lee HE, Lee S et al (2019) Occupational disparities in bladder cancer survival: a population‐based cancer registry study in Japan. Cancer Med 9(3):894–901

  148. Kirby T (2020) Young non-smoker diagnosed with lung cancer. Lancet Respir Med 8(2):141–142

    Article  PubMed  Google Scholar 

  149. Buro-Auriemma LJ, Salit J, Hackett NR et al (2013) Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression. Hum Mol Genet 22(23):4726–4738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Domingo-Vidal M, Whitaker-Menezes D, Martos-Rus C et al (2019) Cigarette smoke induces metabolic reprogramming of the tumor stroma in head and neck squamous cell carcinoma. Mol Cancer Res 17(9):1893–1909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Nyunoya T, Monick MM, Klingelhutz A et al (2006) Cigarette smoke induces cellular senescence. Am J Respir Cell Mol Biol 35(6):681–688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Salem AF, Al-Zoubi MS, Whitaker-Menezes D et al (2013) Cigarette smoke metabolically promotes cancer, via autophagy and premature aging in the host stromal microenvironment. Cell Cycle 12(5):818–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Mortezaee K, Najafi M (2020) Immune system in cancer radiotherapy: resistance mechanisms and therapy perspectives. Crit Rev Oncol/Hematol 157:103180

    Article  Google Scholar 

  154. Weis SM, Cheresh DA (2005) Pathophysiological consequences of VEGF-induced vascular permeability. Nature 437(7058):497

    Article  CAS  PubMed  Google Scholar 

  155. Slepicka PF, Cyrill SL, dos Santos CO (2019) Pregnancy and breast cancer: pathways to understand risk and prevention. Trends Mol Med 25:866–881

    Article  PubMed  Google Scholar 

  156. Ghosh-Choudhary S, Liu J, Finkel T (2020) Metabolic regulation of cell fate and function. Trends Cell Biol 30:201–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Goto H, Shimono Y, Funakoshi Y et al (2019) Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin. Oncogene 38(6):767–779

    Article  CAS  PubMed  Google Scholar 

  158. Reinehr T (2020) Obesity in adolescents and cancer risk: causal relationship or epiphenomenon? Lancet Diabetes Endocrinol 8:179–180

    Article  PubMed  Google Scholar 

  159. Olson OC, Quail DF, Joyce JA (2017) Obesity and the tumor microenvironment. Science 358(6367):1130–1131

    Article  CAS  PubMed  Google Scholar 

  160. Quail DF, Dannenberg AJ (2019) The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol 15(3):139–154

    Article  PubMed  PubMed Central  Google Scholar 

  161. Saha A, Ahn S, Blando J et al (2017) Proinflammatory CXCL12–CXCR4/CXCR7 signaling axis drives myc-induced prostate cancer in obese mice. Can Res 77(18):5158–5168

    Article  CAS  Google Scholar 

  162. Yong C, Stewart GD, Frezza C (2019) Oncometabolites in renal cancer. Nat Rev Nephrol 16:156–172

    Article  PubMed  PubMed Central  Google Scholar 

  163. Baek AE, Yen-Rei AY, He S et al (2017) The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun 8(1):1–11

    Article  Google Scholar 

  164. Wang YY, Attané C, Milhas D et al (2017) Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight 2(4):87489

    Article  PubMed  Google Scholar 

  165. Beyaz S, Mana MD, Roper J et al (2016) High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531(7592):53–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Yang J, Zaman MM, Vlasakov I et al (2019) Adipocytes promote ovarian cancer chemoresistance. Sci Rep 9(1):1–12

    Google Scholar 

  167. Jones SA, Jenkins BJ (2018) Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol 18(12):773–789

    Article  CAS  PubMed  Google Scholar 

  168. Bähr I, Jahn J, Zipprich A et al (2018) Impaired natural killer cell subset phenotypes in human obesity. Immunol Res 66(2):234–244

    Article  PubMed  PubMed Central  Google Scholar 

  169. Albini A, Bruno A, Noonan DM et al (2018) Contribution to tumor angiogenesis from innate immune cells within the tumor microenvironment: implications for immunotherapy. Front Immunol 9:527

    Article  PubMed  PubMed Central  Google Scholar 

  170. Guerrini V, Gennaro ML (2019) Foam cells: one size doesn’t fit all. Trends Immunol 40:1163–1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This research received no external funding.

Author information

Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Keywan Mortezaee

  2. Department of Anatomy, School of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran

    Jamal Majidpoor

Authors
  1. Keywan Mortezaee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jamal Majidpoor
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.M gave the conceptualization. J.M and K.M wrote the initial manuscript. Final revisions were made by K.M. Articles was selected by K.M. Both authors approved the final draft.

Corresponding author

Correspondence to Keywan Mortezaee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The manuscript received the Ethical Code IR.MUK.REC.1399.260 from Kurdistan University of Medical Sciences.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mortezaee, K., Majidpoor, J. Key promoters of tumor hallmarks. Int J Clin Oncol 27, 45–58 (2022). https://doi.org/10.1007/s10147-021-02074-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-021-02074-9

Keywords

Search

Navigation