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Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells

  • Original Article
  • Published:
Tumor Biology

Abstract

Etiological role of viral proteins E6 and E7 of high-risk HPV in cervical carcinogenesis is well established. However, their contribution in chemoresistance and epithelial-mesenchymal transition (EMT) that leads to advanced metastatic lesions and chemoresistance is poorly defined. In the present study, contribution of viral oncoproteins in acquisition of EMT character during onset of chemoresistance was assessed. A chemoresistant cell line (SiHaCR) was developed from an established HPV16-positive cervical cancer cell line, SiHa, by escalating selection pressure of 5-fluorouracil (5-FU). Expression of Survivin, ABCG2, Snail, Slug, Twist, and Vimentin was examined in SiHa and SiHaCR cells by reverse transcriptase-PCR (RT-PCR) and immunoblotting assays. Mesenchymal phenotype in SiHaCR cells was confirmed by assessment of migration and invasion potentials. SiHaCR cells displayed elevated level of functional and molecular markers associated with chemoresistance (Survivin, ABCG2) and EMT (Snail, Slug, Twist, Vimentin) and reduced E-cadherin. SiHaCR also showed increased levels of HPV16 E6 and E7 transcripts. Specific silencing of HPV16 E6, but not E7 using corresponding siRNA, demonstrated a differential involvement of HPV oncogenes in manifestation of EMT. HPV16 E6 silencing resulted in reduction of Slug and Twist expression. However, the expression of Snail and Vimentin was only marginally affected. In contrast, there was an increase in the expression of E-cadherin. A reduced migration and invasion capabilities were observed only in E6-silenced SiHaCR cells, which further confirmed functional contribution of HPV16 E6 in manifestation of EMT. Taken together, our study demonstrated an active involvement of HPV16 E6 in regulation of EMT, which promotes chemoresistance in cervical cancer.

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Abbreviations

5-FU:

5-Fluorouracil

HR-HPV:

High-risk human papillomavirus

EMT:

Epithelial-mesenchymal transition

SP:

Side population

SiHaCR:

Chemoresistant SiHa

References

  1. Jemal A, Simard EP, Dorell C, Noone AM, Markowitz LE, Kohler B, et al. Annual Report to the Nation on the Status of Cancer, 1975–2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013;105(3):175–201.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Perez CA, Grigsby PW, Camel HM, Galakatos AE, Mutch D, Lockett MA. Irradiation alone or combined with surgery in stage IB, IIA, and IIB carcinoma of uterine cervix: update of a nonrandomized comparison. Int J Radiat Oncol Biol Phys. 1995;31(4):703–16.

    Article  CAS  PubMed  Google Scholar 

  3. Vogl SE, Moukhtar M, Kaplan BH. Chemotherapy for advanced cervical cancer with methotrexate, bleomycin, and cis-dichlorodiammineplatinum(II). Cancer Treat Rep. 1979;63(6):1005–6.

    CAS  PubMed  Google Scholar 

  4. Serkies K, Jassem J. Concurrent weekly cisplatin and radiotherapy in routine management of cervical cancer: a report on patient compliance and acute toxicity. Int J Radiat Oncol Biol Phys. 2004;60(3):814–21.

    Article  CAS  PubMed  Google Scholar 

  5. Katsumata N, Hirai Y, Kamiura S, Sugiyama T, Kokawa K, Hatae M, et al. Phase II study of S-1, an oral fluoropyrimidine, in patients with advanced or recurrent cervical cancer. Ann Oncol. 2011;22(6):1353–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Takekuma M, Kasamatsu Y, Kado N, Kuji S, Tanaka A, Takahashi N, et al. Reconsideration of postoperative concurrent chemoradiotherapy with fluorouracil and cisplatin for uterine cervical cancer. J Obstet Gynaecol Res. 2015;41(10):1638–43.

    Article  CAS  PubMed  Google Scholar 

  7. Das BC, Hussain S, Nasare V, Bharadwaj M. Prospects and prejudices of human papillomavirus vaccines in India. Vaccine. 2008;26(22):2669–79.

    Article  PubMed  Google Scholar 

  8. Nagai Y, Toma T, Moromizato H, Maehama T, Asato T, Kariya K, et al. Persistence of human papillomavirus infection as a predictor for recurrence in carcinoma of the cervix after radiotherapy. Am J Obstet Gynecol. 2004;191(6):1907–13.

    Article  PubMed  Google Scholar 

  9. Badaracco G, Savarese A, Micheli A, Rizzo C, Paolini F, Carosi M, et al. Persistence of HPV after radio-chemotherapy in locally advanced cervical cancer. Oncol Rep. 2010;23(4):1093–9.

    PubMed  Google Scholar 

  10. Munger K, Phelps WC, Bubb V, Howley PM, Schlegel R. The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol. 1989;63(10):4417–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wanichwatanadecha P, Sirisrimangkorn S, Kaewprag J, Ponglikitmongkol M. Transactivation activity of human papillomavirus type 16 E6*I on aldo-keto reductase genes enhances chemoresistance in cervical cancer cells. J Gen Virol. 2012;93(Pt 5):1081–92.

    Article  CAS  PubMed  Google Scholar 

  12. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73.

    Article  CAS  PubMed  Google Scholar 

  13. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, et al. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015;527(7579):525–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 2015;527(7579):472–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2(6):442–54.

    Article  CAS  PubMed  Google Scholar 

  16. Hay ED. The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn. 2005;233(3):706–20.

    Article  CAS  PubMed  Google Scholar 

  17. Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994;1198(1):11–26.

    CAS  PubMed  Google Scholar 

  18. Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with snail and E47 repressors. J Cell Sci. 2003;116(Pt 3):499–511.

    Article  CAS  PubMed  Google Scholar 

  19. Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76–83.

    Article  CAS  PubMed  Google Scholar 

  20. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117(7):927–39.

    Article  CAS  PubMed  Google Scholar 

  21. Bagnato A, Rosano L. Understanding and overcoming chemoresistance in ovarian cancer: emerging role of the endothelin axis. Curr Oncol. 2012;19(1):36–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nuti SV, Mor G, Li P, Yin G. TWIST and ovarian cancer stem cells: implications for chemoresistance and metastasis. Oncotarget. 2014;5(17):7260–71.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yang AD, Fan F, Camp RE, Buren G, Liu W, Somcio R, et al. Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res. 2006;12(14):4147–53.

  24. Zhang P, Sun Y, Ma L. ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle. 2015;14(4):481–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang W, Feng M, Zheng G, Chen Y, Wang X, Pen B, et al. Chemoresistance to 5-fluorouracil induces epithelial-mesenchymal transition via up-regulation of snail in MCF7 human breast cancer cells. Biochem Biophys Res Commun. 2012;417(2):679–85.

    Article  CAS  PubMed  Google Scholar 

  26. Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, et al. Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells. 2009;27(9):2059–68.

    Article  CAS  PubMed  Google Scholar 

  27. Haslehurst AM, Koti M, Dharsee M, Nuin P. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC. 2012.

  28. Arumugam T, Ramachandran V, Fournier KF, Wang H, Marquis L, Abbruzzese JL, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009;69(14):5820–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li Q-Q, J-D X, Wang W-J, Cao X-X, Chen Q, Tang F, et al. Twist1-mediated Adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 2009;15(8).

  30. Chen Z, Li S, Huang K, Zhang Q, Wang J, Li X, et al. The nuclear protein expression levels of SNAI1 and ZEB1 are involved in the progression and lymph node metastasis of cervical cancer via the epithelial-mesenchymal transition pathway. Hum Pathol. 2013;44(10):2097–105.

    Article  CAS  PubMed  Google Scholar 

  31. Shibata K, Kajiyama H, Ino K, Terauchi M, Yamamoto E, Nawa A, et al. Twist expression in patients with cervical cancer is associated with poor disease outcome. Ann Oncol. 2008;19(1):81–5.

    Article  CAS  PubMed  Google Scholar 

  32. Zhou XM, Zhang H, Han X. Role of epithelial to mesenchymal transition proteins in gynecological cancers: pathological and therapeutic perspectives. Tumour Biol. 2014;35(10):9523–30.

    Article  CAS  PubMed  Google Scholar 

  33. Cheng YM, Chou CY, Hsu YC, Chen MJ, Wing LY. The role of human papillomavirus type 16 E6/E7 oncoproteins in cervical epithelial-mesenchymal transition and carcinogenesis. Oncol Lett. 2012;3(3):667–71.

    CAS  PubMed  Google Scholar 

  34. Hellner K, Mar J, Fang F, Quackenbush J, Münger K. HPV16 E7 oncogene expression in normal human epithelial cells causes molecular changes indicative of an epithelial to mesenchymal transition. Virology. 2009;391(1):57–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hu D, Zhou J, Wang F, Shi H, Li Y, Li B. HPV-16 E6/E7 promotes cell migration and invasion in cervical cancer via regulating cadherin switch in vitro and in vivo. Arch Gynecol Obstet. 2015;292(6):1345–54.

    Article  CAS  PubMed  Google Scholar 

  36. Qureshi R, Arora H, Rizvi MA. EMT in cervical cancer: its role in tumour progression and response to therapy. Cancer Lett. 2015;356(2 Pt B):321–31.

    Article  CAS  PubMed  Google Scholar 

  37. Chung YM, Park S, Park JK, Kim Y, Kang Y, Yoo YD. Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells. Cancer Lett. 2000;159(1):95–101.

    Article  CAS  PubMed  Google Scholar 

  38. Telford WG, Bradford J, Godfrey W, Robey RW, Bates SE. Side population analysis using a violet-excited cell-permeable DNA binding dye. Stem Cells. 2007;25(4):1029–36.

    Article  CAS  PubMed  Google Scholar 

  39. Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol. 2003;171(7):3863–71.

    Article  CAS  PubMed  Google Scholar 

  40. de Boer MA, Jordanova ES, Kenter GG, Peters AA, Corver WE, Trimbos JB, et al. High human papillomavirus oncogene mRNA expression and not viral DNA load is associated with poor prognosis in cervical cancer patients. Clin Cancer Res. 2007;13(1):132–8.

    Article  PubMed  Google Scholar 

  41. Grespi F, Melino G. P73 and age-related diseases: is there any link with Parkinson disease? Aging (Albany NY). 2012;4(12):923–31.

    Article  CAS  PubMed Central  Google Scholar 

  42. Guan HT, Xue XH, Dai ZJ, Wang XJ, Li A, Qin ZY. Down-regulation of survivin expression by small interfering RNA induces pancreatic cancer cell apoptosis and enhances its radiosensitivity. World J Gastroenterol. 2006;12(18):2901–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lemos C, Kathmann I, Giovannetti E, Calhau C, Jansen G, Peters GJ. Impact of cellular folate status and epidermal growth factor receptor expression on BCRP/ABCG2-mediated resistance to gefitinib and erlotinib. Br J Cancer. 2009;100(7):1120–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rodriguez LG, Wu X, Guan JL. Wound-healing assay. Methods Mol Biol. 2005;294:23–9.

    PubMed  Google Scholar 

  45. Shukla S, Mahata S, Shishodia G, Pandey A, Tyagi A, Vishnoi K, et al. Functional regulatory role of STAT3 in HPV16-mediated cervical carcinogenesis. PLoS One. 2013;8(7):e67849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Scharenberg CW, Harkey MA, Torok-Storb B. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood. 2002;99(2):507–12.

    Article  CAS  PubMed  Google Scholar 

  47. Su PF, Wu FY. Differential suppression of the tumorigenicity of HeLa and SiHa cells by adeno-associated virus. Br J Cancer. 1996;73(12):1533–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM. Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol. 1987;61(4):962–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Harada K, Ferdous T, Ueyama Y. Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes. Int J Oncol. 2014;44(4):1302–8.

    CAS  PubMed  Google Scholar 

  50. Tanaka T, Bai T, Toujima S. Establishment and characterization of monoclonal 5-fluorouracil-resistant cell lines derived from human endometrial adenocarcinoma. Int J Oncol. 2010;37(3):731–6.

    Article  CAS  PubMed  Google Scholar 

  51. Uchibori K, Kasamatsu A, Sunaga M, Yokota S, Sakurada T, Kobayashi E, et al. Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines. Int J Oncol. 2012;40(4):1005–10.

    CAS  PubMed  Google Scholar 

  52. Chen Y, Ke G, Han D, Liang S, Yang G, Wu X. MicroRNA-181a enhances the chemoresistance of human cervical squamous cell carcinoma to cisplatin by targeting PRKCD. Exp Cell Res. 2014;320(1):12–20.

    Article  CAS  PubMed  Google Scholar 

  53. Li Y, Xiao S, Dan L, Xue M. P16(INK4A) is required for cisplatin resistance in cervical carcinoma SiHa cells. Oncol Lett. 2015;9(3):1104–8.

    PubMed  Google Scholar 

  54. Ali AY, Kim J-YY, Pelletier J-FF, Vanderhyden BC, Bachvarov DR, Tsang BK. Akt confers cisplatin chemoresistance in human gynecological carcinoma cells by modulating PPM1D stability. Mol Carcinog. 2015;54(11):1301–14.

    Article  CAS  PubMed  Google Scholar 

  55. Schober M, Jesenofsky R, Faissner R, Krug S, Weidenauer C, Hagmann W, et al. Acquired 5-fluorouracil resistance in human pancreatic carcinoma cells—a paradigm for chemoresistance mechanisms in pancreatic cancer. J Pancreas. 2015;16(3):256–65.

    Google Scholar 

  56. Takahashi K, Tanaka M, Inagaki A, Wanibuchi H, Izumi Y, Miura K, et al. Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line. Int J Oncol. 2013;43(6):1985–91.

    CAS  PubMed  Google Scholar 

  57. Yoo BC, Jeon E, Hong SH, Shin YK, Chang HJ, Park JG. Metabotropic glutamate receptor 4-mediated 5-fluorouracil resistance in a human colon cancer cell line. Clin Cancer Res. 2004;10(12 Pt 1):4176–84.

    Article  CAS  PubMed  Google Scholar 

  58. Zhang X, Yashiro M, Qiu H, Nishii T, Matsuzaki T, Hirakawa K. Establishment and characterization of multidrug-resistant gastric cancer cell lines. Anticancer Res. 2010;30(3):915–21.

    PubMed  Google Scholar 

  59. Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008;8(1):61–70.

    Article  CAS  PubMed  Google Scholar 

  60. Saxena A, Yashar C, Taylor DD, Gercel-Taylor C. Cellular response to chemotherapy and radiation in cervical cancer. Am J Obstet Gynecol. 2005;192(5):1399–403.

    Article  CAS  PubMed  Google Scholar 

  61. Sun R, Jiang B, Qi H, Zhang X, Yang J, Duan J, et al. SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2. Cell Death Dis. 2015;6.

  62. Basu D, Nguyen TT, Montone KT, Zhang G, Wang LP, Diehl JA, et al. Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity. Oncogene. 2010;29(29):4170–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Morata-Tarifa C, Jiménez G, García MA, Entrena JM, Griñán-Lisón C, Aguilera M, et al. Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells. Sci Report. 2016;6.

  64. Lund K, Dembinski JL, Solberg N, Urbanucci A, Mills IG, Krauss S. Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment. PLoS One. 2015;10(4).

  65. Gilles C, Polette M, Piette J, Delvigne AC, Thompson EW, Foidart JM, et al. Vimentin expression in cervical carcinomas: association with invasive and migratory potential. J Pathol. 1996;180(2):175–80.

  66. Zhao W, Zhou Y, Xu H, Cheng Y, Kong B. Snail family proteins in cervical squamous carcinoma: expression and significance. Clin Invest Med. 2013;36(4):E223–33.

    CAS  PubMed  Google Scholar 

  67. Lee M-YY, Chou C-YY, Tang M-JJ, Shen M-RR. Epithelial-mesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14(15):4743–50.

    Article  CAS  Google Scholar 

  68. Liu CY, Chao TK, PH S, Lee HY, Shih YL, HY S, et al. Characterization of LMX-1A as a metastasis suppressor in cervical cancer. J Pathol. 2009;219(2):222–31.

    Article  CAS  PubMed  Google Scholar 

  69. Padilla LA, Leung BS, Carson LF. Evidence of an association between human papillomavirus and impaired chemotherapy-induced apoptosis in cervical cancer cells. Gynecol Oncol. 2002;85(1):59–66.

    Article  CAS  PubMed  Google Scholar 

  70. Duffy CL, Phillips SL, Klingelhutz AJ. Microarray analysis identifies differentiation-associated genes regulated by human papillomavirus type 16. Virology. 2003:E6.

  71. Caberg J-HD, Hubert PM, Begon DY, Herfs MF, Roncarati PJ, Boniver JJ, et al. Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytes. Carcinogenesis. 2008;29(7):1441–7.

    Article  CAS  PubMed  Google Scholar 

  72. Jung Y-SS, Kato I, Kim H-RCR. A novel function of HPV16-E6/E7 in epithelial-mesenchymal transition. Biochem Biophys Res Commun. 2013;435(3):339–44.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The study was supported by research grants from the Department of Science and Technology (DST) and Indian Council of Medical Research (ICMR), Government of India, to ACB, UGC-Junior Research Fellowship to KV [F.2-2/2009 (SA-I)], and grants from ICMR to SM (3/1/13/PDF(2)/2011-HRD), AT (81/3/2009/BMS/Stem Cell), AP (3/2/2/11/2010/NCD-III), and MJ (HIV/50/139/2010-ECD II). Research fellowship from UGC to GV [F.2-2/2009 (SA-I)] and TS (2061430699 22/06/2014(i)EU-V). Authors express their gratitude to Prof. Ravi Mehrotra, Dr. Suresh Hedau, and Dr. R. Suresh Kumar, Institute of Cytology and Preventive Oncology (ICMR) for their support during the conduct of the study.

Author’s contribution

KV—participated in study design, performed major experimental work, and manuscript preparation; SM, AT, AP, MJ, GV, and TS—assisted in experimental work, data analysis, and manuscript preparation; SMS—performed evaluation, data analysis, participated in design of the study, and assisted in critical review of the manuscript; ACB—conceived and designed the study, evaluated data, and critically reviewed, drafted, and communicated the final manuscript. All authors have read and approved the final manuscript.

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Authors and Affiliations

  1. Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), Noida, Uttar Pradesh, India

    Kanchan Vishnoi, Sutapa Mahata, Abhishek Tyagi, Arvind Pandey, Gaurav Verma, Mohit Jadli, Tejveer Singh & Alok C. Bharti

  2. School of Biotechnology, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Kanchan Vishnoi, Gaurav Verma & Sukh Mahendra Singh

  3. Molecular Oncology Laboratory, B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, New Delhi, India

    Abhishek Tyagi

  4. Research Lab, Delhi State Cancer Institute, Delhi, India

    Abhishek Tyagi

  5. Radiation Oncology, Houston Methodist Research Institute, Houston, TX, USA

    Arvind Pandey

  6. Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, 110007, India

    Mohit Jadli, Tejveer Singh & Alok C. Bharti

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  1. Kanchan Vishnoi
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Vishnoi, K., Mahata, S., Tyagi, A. et al. Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells. Tumor Biol. 37, 13137–13154 (2016). https://doi.org/10.1007/s13277-016-5143-6

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