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Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution

  • Xiukun Lin
  • Ammad Ahmad Farooqi
  • Muhammad Zahid Qureshi
  • Mirna Azalea Romero
  • Sobia Tabassum
  • Muhammad Ismail
Review

Abstract

It is becoming characteristically more understandable that within tumor cells, there lies a sub-population of tumor cells with “stem cell” like properties and remarkable ability of self-renewal. Many features of these self-renewing cells are comparable with normal stem cells and are termed as “cancer stem cells”. Accumulating experimentally verified data has started to scratch the surface of spatio-temporally dysregulated intracellular signaling cascades in the biology of prostate cancer stem cells. We partition this multicomponent review into how different signaling cascades operate in cancer stem cells and how bioactive ingredients isolated from natural sources may modulate signaling network.

Keywords

Prostate cancer stem cells Apoptosis Molecular therapeutics Intracellular signaling 

Notes

Acknowledgments

The study was supported in part by National Foundation of Natural Sci. of China (81302906, 81273550, 81573457 and 41306157), as well as Natural Sci. Foundation of Shandong province of China (ZR2014HQ031 and ZR2015HQ027). The authors would like to pay sincere thanks to Prof. F. H. Sarkar who helped in the structuring and conditioning of the review. He helped in English language editing of the manuscript.

References

  1. Bansal N, Farley NJ, Wu L et al (2015) Darinaparsin inhibits prostate tumor-initiating cells and du145 xenografts and is an inhibitor of hedgehog signaling. Mol Cancer Ther 14:23–30CrossRefPubMedGoogle Scholar
  2. Bauderlique-Le Roy H, Vennin C, Brocqueville G et al (2015) Enrichment of human stem-like prostate cells with s-SHIP promoter activity uncovers a role in stemness for the long noncoding RNA H19. Stem Cells Dev 24:1252–1262CrossRefPubMedGoogle Scholar
  3. Bisson I, Prowse DM (2009) WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics. Cell Res 19:683–697CrossRefPubMedGoogle Scholar
  4. Botchkina GI, Zuniga ES, Rowehl RH et al (2013) Prostate cancer stem cell-targeted efficacy of a new-generation taxoid, SBT-1214 and novel polyenolic zinc-binding curcuminoid, CMC2.24. PLoS One 8:e69884CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chang HH, Chen BY, Wu CY et al (2011) Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model. J Biomed Sci 18:6CrossRefPubMedPubMedCentralGoogle Scholar
  6. Chen Q, Cai ZK, Chen YB et al (2015) Poly r(C) binding protein-1 is central to maintenance of cancer stem cells in prostate cancer cells. Cell Physiol Biochem 35:1052–1061CrossRefPubMedGoogle Scholar
  7. Collins AT, Berry PA, Hyde C et al (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951CrossRefPubMedGoogle Scholar
  8. Diaz R, Nguewa PA, Redrado M et al (2015) Sunitinib reduces tumor hypoxia and angiogenesis, and radiosensitizes prostate cancer stem-like cells. Prostate 75:1137–1147CrossRefPubMedGoogle Scholar
  9. Dubrovska A, Kim S, Salamone RJ et al (2009) The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci USA 106:268–273CrossRefPubMedPubMedCentralGoogle Scholar
  10. El-Merahbi R, Liu YN, Eid A et al (2014) Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells. PLoS One 9:e112453CrossRefPubMedPubMedCentralGoogle Scholar
  11. Goksel G, Bilir A, Uslu R et al (2014) WNT1 gene expression alters in heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+ prostate cancer stem cell spheroids. J BUON 19:207–214PubMedGoogle Scholar
  12. Gu G, Yuan J, Wills M et al (2007) Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res 67:4807–4815CrossRefPubMedGoogle Scholar
  13. Jiang Y, Dai J, Zhang H et al (2013) Activation of the Wnt pathway through AR79, a GSK3β inhibitor, promotes prostate cancer growth in soft tissue and bone. Mol Cancer Res 11:1597–1610CrossRefPubMedGoogle Scholar
  14. Kim W, Barron DA, San Martin R et al (2014) RUNX1 is essential for mesenchymal stem cell proliferation and myofibroblast differentiation. Proc Natl Acad Sci USA 111:16389–16394CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kroon J, in’t Veld LS, Buijs JT et al (2014) Glycogen synthase kinase-3β inhibition depletes the population of prostate cancer stem/progenitor-like cells and attenuates metastatic growth. Oncotarget 5:8986–8994CrossRefPubMedPubMedCentralGoogle Scholar
  16. Li H, Zhou J, Miki J et al (2008) Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells. Exp Cell Res 314:92–102CrossRefPubMedGoogle Scholar
  17. Li L, Dang Q, Xie H et al (2015) Infiltrating mast cells enhance prostate cancer invasion via altering LncRNA-HOTAIR/PRC2-androgen receptor (AR)-MMP9 signals and increased stem/progenitor cell population. Oncotarget 6:14179–14190CrossRefPubMedPubMedCentralGoogle Scholar
  18. Liang J, Li Y, Daniels G et al (2015) LEF1 Targeting EMT in prostate cancer invasion is regulated by miR-34a. Mol Cancer Res 13:681–688CrossRefPubMedPubMedCentralGoogle Scholar
  19. Lin SJ, Yang DR, Wang N et al (2015) TR4 nuclear receptor enhances prostate cancer initiation via altering the stem cell population and EMT signals in the PPARG-deleted prostate cells. Oncoscience 2:142–150CrossRefPubMedPubMedCentralGoogle Scholar
  20. Miki J, Furusato B, Li H et al (2007) Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res 67:3153–3161CrossRefPubMedGoogle Scholar
  21. Nadendla SK, Hazan A, Ward M et al (2011) GLI1 confers profound phenotypic changes upon LNCaP prostate cancer cells that include the acquisition of a hormone independent state. PLoS One 6:e20271CrossRefPubMedPubMedCentralGoogle Scholar
  22. Ni J, Cozzi PJ, Hao JL et al (2014) CD44 variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance. Prostate 74:602–617CrossRefPubMedGoogle Scholar
  23. Özdemir BC, Hensel J, Secondini C et al (2014) The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches. PLoS One 9:e114530CrossRefPubMedPubMedCentralGoogle Scholar
  24. Patrawala L, Calhoun T, Schneider-Broussard R et al (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25:1696–1708CrossRefPubMedGoogle Scholar
  25. Patrawala L, Calhoun-Davis T, Schneider-Broussard R et al (2007) Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+ alpha2beta1+ cell population is enriched in tumor-initiating cells. Cancer Res 67:6796–6805CrossRefPubMedGoogle Scholar
  26. Peng YC, Levine CM, Zahid S et al (2013) Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration. Proc Natl Acad Sci USA 110:20611–20616CrossRefPubMedPubMedCentralGoogle Scholar
  27. Pollock CB, McDonough S, Wang VS et al (2014) Strigolactone analogues induce apoptosis through activation of p38 and the stress response pathway in cancer cell lines and in conditionally reprogrammed primary prostate cancer cells. Oncotarget 5:1683–1698CrossRefPubMedPubMedCentralGoogle Scholar
  28. Qin J, Liu X, Laffin B et al (2012) The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 10:556–569CrossRefPubMedPubMedCentralGoogle Scholar
  29. Rabbani SA, Arakelian A, Farookhi R (2013) LRP5 knockdown: effect on prostate cancer invasion growth and skeletal metastasis in vitro and in vivo. Cancer Med 2:625–635PubMedPubMedCentralGoogle Scholar
  30. Ribatti D, Mangialardi G, Vacca A (2006) Stephen Paget and the ‘seed and soil’ theory of metastatic dissemination. Clin Exp Med 6:145–149CrossRefPubMedGoogle Scholar
  31. Shang Z, Cai Q, Zhang M et al (2015) A switch from CD44+ cell to EMT cell drives the metastasis of prostate cancer. Oncotarget 6:1202–1216CrossRefPubMedPubMedCentralGoogle Scholar
  32. Soner BC, Aktug H, Acikgoz E et al (2014) Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol. Int J Mol Med 34:1249–1256PubMedPubMedCentralGoogle Scholar
  33. Statkiewicz M, Maryan N, Lipiec A et al (2014) The role of the SHH gene in prostate cancer cell resistance to paclitaxel. Prostate 74:1142–1152CrossRefPubMedGoogle Scholar
  34. Tang SN, Singh C, Nall D et al (2010) The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J Mol Signal 5:14CrossRefPubMedPubMedCentralGoogle Scholar
  35. van den Hoogen C, van der Horst G, Cheung H et al (2011) The aldehyde dehydrogenase enzyme 7A1 is functionally involved in prostate cancer bone metastasis. Clin Exp Metastasis 28:615–625CrossRefPubMedPubMedCentralGoogle Scholar
  36. Wang P, Henning SM, Heber D et al (2015) Sensitization to docetaxel in prostate cancer cells by green tea and quercetin. J Nutr Biochem 26:408–415CrossRefPubMedPubMedCentralGoogle Scholar
  37. Yang J, Wahdan-Alaswad R, Danielpour D (2009) Critical role of Smad2 in tumor suppression and transforming growth factor-beta-induced apoptosis of prostate epithelial cells. Cancer Res 69:2185–2190CrossRefPubMedPubMedCentralGoogle Scholar
  38. Zhang L, Li L, Jiao M et al (2012) Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway. Cancer Lett 323:48–57CrossRefPubMedGoogle Scholar
  39. Zhao RC, Zhu YS, Shi Y et al (2008) New hope for cancer treatment: exploring the distinction between normal adult stem cells and cancer stem cells. Pharmacol Ther 119:74–82CrossRefPubMedGoogle Scholar
  40. Zhou Y, Yang J, Zhang R et al (2015) Combination therapy of prostate cancer with HPMA copolymer conjugates containing PI3K/mTOR inhibitor and docetaxel. Eur J Pharm Biopharm 89:107–115CrossRefPubMedPubMedCentralGoogle Scholar
  41. Zhu G, Zhou J, Song W et al (2013) Role of GLI-1 in epidermal growth factor-induced invasiveness of ARCaPE prostate cancer cells. Oncol Rep 30:904–910PubMedGoogle Scholar
  42. Zuo J, Guo Y, Peng X et al (2015) Inhibitory action of pristimerin on hypoxia-mediated metastasis involves stem cell characteristics and EMT in PC-3 prostate cancer cells. Oncol Rep 33:1388–1394PubMedGoogle Scholar

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2016

Authors and Affiliations

  • Xiukun Lin
    • 1
  • Ammad Ahmad Farooqi
    • 2
  • Muhammad Zahid Qureshi
    • 3
  • Mirna Azalea Romero
    • 4
  • Sobia Tabassum
    • 5
  • Muhammad Ismail
    • 6
  1. 1.Department of PharmacologyCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Laboratory for Translational Oncology and Personalized Medicine, RLMCLahorePakistan
  3. 3.Department of ChemistryGCULahorePakistan
  4. 4.Laboratorio de Investigación Clínica, Unidad Académica de Medicina, Universidad Autónoma de GuerreroAcapulcoMéxico
  5. 5.Department of Bioinformatics and BiotechnologyInternational Islamic UniversityIslamabadPakistan
  6. 6.Institute of Biomedical and Genetic Engineering (IBGE)IslamabadPakistan

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