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Cervical Cancer Stem Cells and Their Association with Human Papillomavirus: Are They Ready as Anticancer Targets?

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Multi-Targeted Approach to Treatment of Cancer

Abstract

Despite well-established human papillomavirus (HPV)-mediated etiology of cervical cancer, it has remained a major cause of cancer-related mortality of women from developing countries. Factors that contribute to high mortality rate primarily include disease diagnosis in advanced stages and failure of conventional treatment offered to these patients resulting in tumor relapse. Cancer stem cells (CSCs), in spite of controversies on their existence, are emerging as important players that initiate and maintain the tumor phenotype, govern tumor relapse, and chemo-/radioresistance, and thus considered as main factor that decides the treatment outcome. Recent studies provide evidence not only for presence of CSCs but also involvement of stemness-related signaling pathways and transcription factors in cervical cancer tissues and cell lines. The investigations made till date, however, lack evidence demonstrating a direct involvement of HPV oncoprotein(s) in modulation of CSC properties, relative proportions, or stem cell signaling in tumor tissues. Available literature, however, does support the involvement of HPV in these events. In the present article, we attempt to collate available data that demonstrates presence of CSC in cervical cancer, specific markers used to derive cervical CSC, and explored possibility of a potential cross talk of HPV oncoproteins with CSC signaling particularly with the known self-renewal signaling pathways like Notch, Hedgehog (Hh), and Wnt as well as stemness-related transcription factor like Oct4, Nanog, Sox2, and STAT3 that maintain CSC phenotype and functionality. Overall, present article provides rationale for detailed investigation of HPV role in regulation of CSC in cervical tumor tissues for an effective targeting of refractory lesions and to prevent tumor relapse.

Grant Support

The study was supported by extramural and intramural research grants from Department Science and Technology (DST) and Indian Council of Medical Research (ICMR), Government of India, to ACB (IRIS2013-2762) and BCD Grant from CSIR-UGC to KV [F.2-2/2009 (SA-I)] and ICMR-Senior Research Fellowship to AT (No. 81/3/2009/BMS/Stem Cell).

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Abbreviations

ALDH:

Aldehyde dehydrogenase

CSCs:

Cancer stem cells

Hh:

Hedgehog

HPV:

Human papillomavirus

HR:

High risk

SCJ:

Squamocolumnar junction

SP:

Side population

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Authors and Affiliations

  1. Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, UP, 201301, India

    Kanchan Vishnoi, Abhishek Tyagi & Alok C. Bharti

  2. School of Biotechnology, Banaras Hindu University, Varanasi, UP, India

    Kanchan Vishnoi & Sukh Mahendra Singh

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

    Abhishek Tyagi & Bhudev C. Das

Authors
  1. Kanchan Vishnoi
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  2. Abhishek Tyagi
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  3. Sukh Mahendra Singh
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  4. Bhudev C. Das
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  5. Alok C. Bharti
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Corresponding author

Correspondence to Alok C. Bharti .

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Editors and Affiliations

  1. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Varsha Gandhi

  2. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Kapil Mehta

  3. Delhi State Cancer Institute (East), Delhi, India

    Rajesh Grover

  4. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Sen Pathak

  5. Department of Bioimmunotherapy, Section of Cytokine Research, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Bharat B. Aggarwal

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Vishnoi, K., Tyagi, A., Singh, S.M., Das, B.C., Bharti, A.C. (2015). Cervical Cancer Stem Cells and Their Association with Human Papillomavirus: Are They Ready as Anticancer Targets?. In: Gandhi, V., Mehta, K., Grover, R., Pathak, S., Aggarwal, B. (eds) Multi-Targeted Approach to Treatment of Cancer. Adis, Cham. https://doi.org/10.1007/978-3-319-12253-3_24

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