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

Content Provider	Springer Nature Link
Author	Vishnoi, Kanchan Mahata, Sutapa Tyagi, Abhishek Pandey, Arvind Verma, Gaurav Jadli, Mohit Singh, Tejveer Singh, Sukh Mahendra Bharti, Alok C.
Copyright Year	2016
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.
Starting Page	13137
Ending Page	13154
Page Count	18
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	10
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-07-24
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Cervical cancer Human papillomavirus (HPV) Chemoresistance Epithelial-mesenchymal transition (EMT) 5-fluorouracil (5-FU) Invasion Migration Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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