Skip to main content
SpringerLink
Log in

Rab5C enhances resistance to ionizing radiation in rectal cancer

  • Original Article
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Rectal cancer represents one third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment reducing the risk of local recurrence. However, a pathologic complete response is only achieved in 10–40% of cases and the mechanisms associated with resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed and compared with residual tumor tissues removed by surgery after neoadjuvant therapy. Three proteins, Ku70, Ku80, and Rab5C, exhibited a significant increase in expression after chemoradiation. To better understand the role of these proteins in therapy resistance, a rectal adenocarcinoma cell line was irradiated to generate a radiotherapy-resistant lineage. These cells overexpressed the same three proteins identified in the tissue samples. Furthermore, radiotherapy resistance in this in vitro model was found to involve modulation of epidermal growth factor receptor (EGFR) internalization by Rab5C in response to irradiation, affecting expression of the DNA repair proteins, Ku70 and Ku80, and cell resistance. Taken together, these findings indicate that EGFR and Rab5C are potential targets for the sensitization of rectal cancer cells and they should be further investigated.

Key messages

• Rab5C orchestrates a mechanism of radioresistance in rectal adenocarcinoma cell.

• Rab5C modulates EGFR internalization and its relocalization to the nucleus.

• In the nucleus, EGFR can modulate the expression of the DNA repair proteins, Ku70 and Ku80.

• Rab5C, Ku70, and Ku80 are overexpressed in tumor tissues that contain tumor cells that are resistant to chemoradiation treatment.

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

Figure 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

References

  1. Tamas K, Walenkamp AM, de Vries EGE, van Vugt MA, Beets-Tan RG, van Etten B, et al. (2015) Rectal and colon cancer: Not just a different anatomic site. Cancer Treat Rev [Internet]. Elsevier Ltd; Available from: http://linkinghub.elsevier.com/retrieve/pii/S0305737215001292

  2. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  CAS  PubMed  Google Scholar 

  3. Bosset J, Collette L, Callais G, Mineur L, Maingon P, Radosevic-Jelic L et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123

    Article  CAS  PubMed  Google Scholar 

  4. Maas M, Nelemans P, Valentini V, Das P, Rödel C, Kuo L et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844

    Article  PubMed  Google Scholar 

  5. Wasmuth HH, Rekstad LC, Tranø G (2015) The outcome and the frequency of pathological complete response after neoadjuvant radiotherapy in curative resections for advanced rectal cancer: a population-based study. Color Dis [Internet];n/a-n/a. Available from: http://doi.wiley.com/10.1111/codi.13072

  6. Huber SM, Butz L, Stegen B, Klumpp D, Braun N, Ruth P et al (2013) Ionizing radiation, ion transports, and radioresistance of cancer cells. Front Physiol 4:1–14

    Article  Google Scholar 

  7. Liccardi G, Hartley J, Hochhauser D (2011) EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment. Cancer Res 71:1103–1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dittmann K, Mayer C, Rodemann H-P (2005) Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol 76:157–161 Available from: http://linkinghub.elsevier.com/retrieve/pii/S0167814005002513

    Article  CAS  PubMed  Google Scholar 

  9. Schmidt-Ullrich RK, Mikkelsen RB, Dent P, Todd DG, Valerie K, Kavanagh BD, Contessa JN, Rorrer WK, Chen PB (1997) Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene 15:1191–1197

    Article  CAS  PubMed  Google Scholar 

  10. Dittmann K, Mayer C, Kehlbach R, Rodemann HP (2008) Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK. Mol Cancer 7:69 Available from: http://www.molecular-cancer.com/content/7/1/69

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Dittmann K, Mayer C, Fehrenbacher B, Schaller M, Raju U, Milas L, Chen DJ, Kehlbach R, Rodemann HP (2005) Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem 280:31182–31189

    Article  CAS  PubMed  Google Scholar 

  12. Begg AC, Stewart FA, Vens C (2011) Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer [Internet]. Nature Publishing Group;11:239–53. Available from: http://www.nature.com/doifinder/10.1038/nrc3007

    Article  CAS  PubMed  Google Scholar 

  13. Vizoso M, Ferreira HJ, Lopez-Serra P, Carmona FJ, Martínez-Cardús A, Girotti MR, Villanueva A, Guil S, Moutinho C, Liz J, Portela A, Heyn H, Moran S, Vidal A, Martinez-Iniesta M, Manzano JL, Fernandez-Figueras MT, Elez E, Muñoz-Couselo E, Botella-Estrada R, Berrocal A, Pontén F, Oord J, Gallagher WM, Frederick DT, Flaherty KT, McDermott U, Lorigan P, Marais R, Esteller M (2015) Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nat Med 21:741–750 Available from: http://www.nature.com.gate1.inist.fr/nm/journal/v21/n7/full/nm.3863.html

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen P-I, Kong C, Su X, Stahl PD (2009) Rab5 isoforms differentially regulate the trafficking and degradation of epidermal growth factor receptors. J Biol Chem 284:30328–30338 Available from: http://www.jbc.org/cgi/doi/10.1074/jbc.M109.034546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Tsuno N, Kazama S, Kitayama J, Suzuki N, Nagawa H (2002) The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer 95:1199–1205

    Article  PubMed  Google Scholar 

  16. Mazzarelli P, Parrella P, Seripa D, Signori E, Perrone G, Rabitti C, Borzomati D, Gabbrielli A, Matera MG, Gravina C, Caricato M, Poeta ML, Rinaldi M, Valeri S, Coppola R, Fazio VM (2005) DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor. World J Gastroenterol 11:6694–6700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang Y, Li H, Li Y, Min J (2011) The expression and clinical significance of RABEX-5 and RAB5 in breast cancer. Sichuan Da Xue Xue Bao Yi Xue Ban 42:185–189. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21500550

    PubMed  Google Scholar 

  18. Zhao Z, Liu X-F, Wu H-C, Zou S-B, Wang J-Y, Ni P-H et al (2010) Rab5a overexpression promoting ovarian cancer cell proliferation may be associated with APPL1-related epidermal growth factor signaling pathway. Cancer Sci 101:1454–1462 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20412119

    Article  CAS  PubMed  Google Scholar 

  19. Li Y, Meng X, Feng H, Zhang G, Liu C, Li P (1999) Over-expression of the RAB5 gene in human lung adenocarcinoma cells with high metastatic potential. Chin Med Sci J 14:96–101 Available from: http://europepmc.org/abstract/med/12901617

    CAS  PubMed  Google Scholar 

  20. O’Driscoll M, Jeggo PA (2006) The role of double-strand break repair—insights from human genetics. Nat Rev Genet 7:45–54 Available from: http://www.nature.com/doifinder/10.1038/nrg1746

    Article  PubMed  CAS  Google Scholar 

  21. Hu L, Wu QQ, Wang WB, Jiang HG, Yang L, Liu Y, Yu HJ, Xie CH, Zhou YF, Zhou FX (2013) Suppression of Ku80 correlates with radiosensitivity and telomere shortening in the U2OS telomerase-negative osteosarcoma cell line. Asian Pac J Cancer Prev 14:795–799

    Article  PubMed  Google Scholar 

  22. Koike M, Yutoku Y, Koike A (2011) Establishment of ku70-deficient lung epithelial cell lines and their hypersensitivity to low-dose x-irradiation. J Vet Med Sci:73, 549–554 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21160137

    Article  CAS  PubMed  Google Scholar 

  23. Veuger SJ, Curtin NJ, Richardson CJ, Smith GCM, Durkacz BW (2003) Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and. Cancer Res ;63:6008–15

  24. Lin SY, Makino K, Xia W, Matin A, Wen Y, Kwong KY, Bourguignon L, Hung MC (2001) Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 3:802–808

    Article  CAS  PubMed  Google Scholar 

  25. Lo H-W, Xia W, Wei Y, Ali-Seyed M, Huang S-F, Hung M-C (2005) Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer Res 65:338–348

    CAS  PubMed  Google Scholar 

  26. Xia W, Wei Y, Du Y, Liu J, Chang B, Yu Y-L et al (2009) Nuclear expression of epidermal growth factor receptor is a novel prognostic value in patients with ovarian cancer. Mol Carcinog 48:610–617 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2718429&tool=pmcentrez&rendertype=abstract

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chen P-I, Schauer K, Kong C, Harding AR, Goud B, Stahl PD (2014) Rab5 isoforms orchestrate a “division of labor” in the endocytic network; Rab5C modulates RAC-mediated cell motility. PLoS One 9:e90384 Available from: http://dx.plos.org/10.1371/journal.pone.0090384

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Wheeler DB, Zoncu R, Root DE, Sabatini DM, Sawyers CL (2015) Identification of an oncogenic RAB protein. Science

  29. Zeigerer A, Gilleron J, Bogorad RL, Marsico G, Nonaka H, Seifert S, Epstein-Barash H, Kuchimanchi S, Peng CG, Ruda VM, Conte-Zerial PD, Hengstler JG, Kalaidzidis Y, Koteliansky V, Zerial M (2012) Rab5 is necessary for the biogenesis of the endolysosomal system in vivo. Nature. Nature Publishing Group;485:465–70. Available from: https://doi.org/10.1038/nature11133

    Article  CAS  PubMed  Google Scholar 

  30. Hoepfner S, Severin F, Cabezas A, Habermann B, Runge A, Gillooly D, Stenmark H, Zerial M (2005) Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 121:437–450 Available from: http://linkinghub.elsevier.com/retrieve/pii/S0092867405001625

    Article  CAS  PubMed  Google Scholar 

  31. Barbieri MA, Roberts RL, Gumusboga A, Highfield H, Alvarez-Dominguez C, Wells A, Stahl PD (2000) Epidermal growth factor and membrane trafficking. J Cell Biol 151:539–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gurkan C, Lapp H, Alory C, Su AI, Hogenesch JB, Balch WE (2005) Large-scale profiling of Rab GTPase trafficking networks: the membrome. Mol Biol Cell 16:3847–3864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Onodera Y, Nam J-M, Hashimoto A, Norman JC, Shirato H, Hashimoto S et al (2012) Rab5c promotes AMAP1-PRKD2 complex formation to enhance 1 integrin recycling in EGF-induced cancer invasion. J Cell Biol 197:983–996 Available from: http://www.jcb.org/cgi/doi/10.1083/jcb.201201065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S et al (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67:2643–2648 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17363584

    Article  CAS  PubMed  Google Scholar 

  35. Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765 Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0804385

    Article  CAS  PubMed  Google Scholar 

  36. Kasper S, Breitenbuecher F, Reis H, Brandau S, Worm K, Köhler J, Paul A, Trarbach T, Schmid KW, Schuler M (2013) Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade. Oncogene 32:2873–2881 Available from: http://www.nature.com/articles/onc2012302

    Article  CAS  PubMed  Google Scholar 

  37. Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, Batra SK (2012) Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 16:15–31 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22239438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tanos B, Pendergast AM (2006) Abl tyrosine kinase regulates endocytosis of the epidermal growth factor receptor. J Biol Chem 281:32714–32723 Available from: http://www.jbc.org/lookup/doi/10.1074/jbc.M603126200

    Article  CAS  PubMed  Google Scholar 

  39. Sousa LP, Lax I, Shen H, Ferguson SM, Camilli PD, Schlessinger J (2012) Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membrane. Proc Natl Acad Sci USA 109:4419–4424 Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.1200164109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bazzani L, Donnini S, Giachetti A, Christofori G, Ziche M (2018) PGE2 mediates EGFR internalization and nuclear translocation via caveolin endocytosis promoting its transcriptional activity and proliferation in human NSCLC cells. Oncotarget. Available from: http://www.oncotarget.com/fulltext/24499

  41. Al-Akhrass H, Naves T, Vincent F, Magnaudeix A, Durand K, Bertin F et al (2017) Sortilin limits EGFR signaling by promoting its internalization in lung cancer. Nat Commun 8:1182 Available from: http://www.nature.com/articles/s41467-017-01172-5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Walsh AM, Lazzara MJ (2013) Regulation of EGFR trafficking and cell signaling by Sprouty2 and MIG6 in lung cancer cells. J Cell Sci 126:4339–4348 Available from: http://jcs.biologists.org/cgi/doi/10.1242/jcs.123208

    Article  CAS  PubMed  Google Scholar 

  43. Berg KCG, Eide PW, Eilertsen IA, Johannessen B, Bruun J, Danielsen SA et al (2017) Multi-omics of 34 colorectal cancer cell lines—a resource for biomedical studies. Mol Cancer 16:116 Available from: http://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-017-0691-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Huang S-M, Bock JM, Harari PM (1999) Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 59:1935–1940 Available from: http://cancerres.aacrjournals.org.ezproxy.auckland.ac.nz/content/59/8/1935

    CAS  PubMed  Google Scholar 

  45. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Article  CAS  PubMed  Google Scholar 

  46. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK et al (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11:21–28 Available from: http://linkinghub.elsevier.com/retrieve/pii/S1470204509703110

    Article  CAS  PubMed  Google Scholar 

  47. Dewdney A, Cunningham D, Tabernero J, Capdevila J, Glimelius B, Cervantes A et al (2012) Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol 30:1620–1627 Available from: http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2011.39.6036

    Article  CAS  PubMed  Google Scholar 

  48. Sclafani F, Gonzalez D, Cunningham D, Hulkki Wilson S, Peckitt C, Giralt J, Glimelius B, Roselló Keränen S, Wotherspoon A, Brown G, Tait D, Oates J, Chau I (2014) RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial. Eur J Cancer 50:1430–1436

    Article  CAS  PubMed  Google Scholar 

  49. Jo U, Park KH, Whang YM, Sung JS, Won NH, Park JK et al (2014) EGFR endocytosis is a novel therapeutic target in lung cancer with wild-type EGFR. Oncotarget 5:1265–1278 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4012721&tool=pmcentrez&rendertype=abstract

    PubMed  PubMed Central  Google Scholar 

  50. Hong L, Simons P, Waller A, Strouse J, Surviladze Z, Ursu O et al. A small molecule pan-inhibitor of Ras-superfamily GTPases with high efficacy towards Rab7. Probe Reports from the NIH Molecular Libraries Program [Internet]. National Center for Biotechnology Information, Bethesda

  51. Hong L, Guo Y, BasuRay S, Agola JO, Romero E, Simpson DS et al (2015) A Pan-GTPase Inhibitor as a Molecular Probe. PLoS One 10:e0134317 Available from: http://dx.plos.org/10.1371/journal.pone.0134317

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Marina França de Resende from the Department of Anatomic Pathology, A.C. Camargo Cancer Center, for help with the IHC staining. We also acknowledge the A.C. Camargo Biobank in the name of Dr. Antônio Hugo Campos and Dr. Dirce Carraro for providing great quality tumor samples and complete patient data. This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; VRM 2009/14027-2), the National Institute for Science and Technology in Oncogenomics (INCITO) and CAPES. Fellowships from FAPESP were awarded to A.R.B (2013/04913-0), M.V.S.D. (2010/19200-1), F.G (2013/23285-8), and T.C.L (2011/18718-0).

Funding

This study received funding from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; VRM 2009/14027-2) and the National Institute for Science and Technology in Oncogenomics (INCITO).

Author information

Authors and Affiliations

  1. International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440, Liberdade, São Paulo/SP, 01508-010, Brazil

    Antuani Rafael Baptistella, Michele Christine Landemberger, Marcos Vinicios Salles Dias, Fernanda Salgueiredo Giudice, Bruna Roz Rodrigues, Edson Kuatelela Cassinela, Tonielli Cristina Lacerda, Fabio Albuquerque Marchi, Samuel Aguiar Jr & Vilma Regina Martins

  2. National Institute for Science and Technology in Oncogenomics – INCITO (CNPq/MCT/FAPESP/CAPES), São Paulo, Brazil

    Antuani Rafael Baptistella, Michele Christine Landemberger, Marcos Vinicios Salles Dias, Fernanda Salgueiredo Giudice, Bruna Roz Rodrigues, Edson Kuatelela Cassinela, Tonielli Cristina Lacerda, Fabio Albuquerque Marchi, Maria Dirlei Begnami, Samuel Aguiar Jr & Vilma Regina Martins

  3. Department of Medical Physics, A.C.Camargo Cancer Center, São Paulo, Brazil

    Petrus Paulo Combas Eufrazio da Silva

  4. Brazilian Biosciences National Laboratory—LNBio, Campinas, Brazil

    Adriana Franco Paes Leme

  5. Department of Anatomic Pathology, A.C.Camargo Cancer Center, São Paulo, Brazil

    Maria Dirlei Begnami

  6. Department of Pelvic Surgery, A.C.Camargo Cancer Center, São Paulo, Brazil

    Samuel Aguiar Jr

Authors
  1. Antuani Rafael Baptistella
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michele Christine Landemberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcos Vinicios Salles Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernanda Salgueiredo Giudice
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bruna Roz Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Petrus Paulo Combas Eufrazio da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Edson Kuatelela Cassinela
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tonielli Cristina Lacerda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fabio Albuquerque Marchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Adriana Franco Paes Leme
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maria Dirlei Begnami
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Samuel Aguiar Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Vilma Regina Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ARB: Study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript. MCL: performed experiments and analysis and interpretation of data. MVSD: Study concept and design, analysis and interpretation of data; drafting of the manuscript. FSG: Study concept and design, analysis and interpretation of data; drafting of the manuscript. BRR: Analysis and interpretation of data; drafting of the manuscript. PPCES: Study concept and design; performed the ionizing irradiation assay. EKC: Study concept and design, analysis and interpretation of data. TCL: Study concept and design, analysis and interpretation of data. FAM: Analysis and interpretation of data; bioinformatics analysis and drafting of the manuscript. AFPL: Study concept and design, performed the proteomic analysis and interpretation of data. MDB: Study concept and design, immunohistochemistry analysis and analysis and interpretation of data. SAJ: Study concept and design; analysis and interpretation of data; critical revision of the manuscript. VRM: Study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Samuel Aguiar Jr or Vilma Regina Martins.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Research Ethics Committee (CEP) of A.C. Camargo Cancer Center (243.157) and all patients gave their informed consent prior to their inclusion in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s note

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

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baptistella, A.R., Landemberger, M.C., Dias, M.V.S. et al. Rab5C enhances resistance to ionizing radiation in rectal cancer. J Mol Med 97, 855–869 (2019). https://doi.org/10.1007/s00109-019-01760-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-019-01760-6

Keywords

Search

Navigation