Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity
Authors: Abhishek Tyagi
Kanchan Vishnoi
Alok C Bharti
Yogesh Srivastava
Bal Gangadhar Roy
Harsimrut Kaur
Bhudev C Das
Journal: Scientific reports (2017)
Discipline: Multidisciplinary
Keywords: Transcription factor AP-1; HPV-mediated cervical carcinogenesis; chemo-radio-resistance; cervical cancer stem-like cells; CaCxSLCs
Affiliations: Molecular Oncology Laboratory, B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, Delhi, 110007, India., Division of Molecular Oncology, National Institute of Cancer Prevention and Research (NICPR), Noida, 201301, Uttar Pradesh, India., Stem Cell and Cancer Research Lab, Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, 201313, India., Institute of Nuclear Medicine and Allied Sciences, Defence Research Development Organization, Delhi, 110 054, India., Molecular Oncology Laboratory, B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, Delhi, 110007, India. ., Stem Cell and Cancer Research Lab, Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, 201313, India. ., Division of Molecular Oncology, National Institute of Cancer Prevention and Research (NICPR), Noida, 201301, Uttar Pradesh, India. ., Molecular Oncology Laboratory, Department of Zoology, University of Delhi, Delhi, 110007, India. .

Abstract:  Transcription factor AP-1 plays a central role in HPV-mediated cervical carcinogenesis. AP-1 has also been implicated in chemo-radio-resistance but the mechanism(s) remained unexplored. In the present study, cervical cancer stem-like cells (CaCxSLCs) isolated and enriched from cervical cancer cell lines SiHa and C33a demonstrated an elevated AP-1 DNA-binding activity in comparison to non-stem cervical cancer cells. Upon UV-irradiation, CaCxSLCs showed a UV exposure duration-dependent higher proliferation and highly increased AP-1 activity whereas it was completely abolished in non-stem cancer cells. CaCxSLCs also showed differential overexpression of c-Fos and c-Jun at transcript as well as in protein level. The loss of AP-1 activity and expression was accompanied by decrease in cell viability and proliferation in UV-irradiated non-stem cancer cells. Interestingly, CaCxSLCs treated with curcumin prior to UV-irradiation abolished AP-1 activity and a concomitant reduction in SP cells leading to abrogation of sphere forming ability, loss of proliferation, induction of apoptosis and the cells were poorly tumorigenic. The curcumin pre-treatment abolished the expression of c-Fos and c-Jun but upregulated Fra-1 expression in UV-irradiated CaCxSLCs. Thus, the study suggests a critical role of AP-1 protein in the manifestation of radioresistance but targeting with curcumin helps in radiosensitizing CaCxSLCs through upregulation of Fra-1. 

Retracted: No

PubPeer comments:
 Image manipulated and recycled from a previous paper. Cells and treatments are different.  , 
 #1 Dear Pubpeer, Thank you for notifying us about this error in our paper on u201cCervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activityu201d, I am surprised that the figures published in 2016 is identical to that shown in publication in 2017 with wrong labelling. I have contacted the first author (my graduate student, Abhishek Tyagi) and learned that indeed the wrong image was inadvertently included when he assembled the final figures. Undeniably, this we overlooked and we have no hesitation now to apologize and correct it. Please see below for the corrected Panel D of Figure 1. We emphasize that this figure replacement does not affect the validity of the data, its interpretation and conclusions drawn, or any other aspect of the published paper. Nevertheless, we will contact the Nature Editorial Office immediately to let them know about this error and if they wish to correct it in the online version of the paper. Warm regards, Bhudev Das , 
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