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Insulin growth factor-1 pathway in cervical carcinoma cancer stem cells

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Abstract

Cancer stem cells (CSC) drive tumour progression and are implicated in relapse and resistance to conventional cancer therapies. Identification of differentially expressed genes by gene expression (GEP) profiling may help identify the differentially activated signalling pathways in cancer stem cells as opposed to bulk tumour cells which will provide new insights into cancer stem cell biology and aid in identification of novel therapeutic targets. Our study focused on the inhibition of CSC from cervical cancer cell lines by targeting insulin-like growth factor (IGF), which was identified by differential GEP. Targeted inhibition of IGF-1 by JB-1 trifluoroacetate (inhibitor of IGF) was carried out in SiHa, RSBS-14 and RSBS-43 cervical cancer derived cell lines. Effect of cisplatin was also evaluated. Inhibition of IGF-1 signalling was confirmed by demonstration of reduction in p-Akt levels. The cell biological effects of IGF-1 inhibition included an increase in G2M/S fraction, increased apoptosis and decreased invasive ability. JB-1 and cisplatin showed synergism. However, transcript levels of stemness and EMT markers showed variable levels following IGF inhibition. Overall, this proof-of-concept study has shown that IGF-1 is an attractive target for inhibition of CSC in invasive cervical cancer.

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Data Availability

The link for public data https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120270

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Funding

Department of Science and Technology, Govt. of India, grant reference no.- DST No: D.O. No.-SR/SO/HS-0166/2010; PGI Intramural Research Scheme No. 71/5-EDU/12/1363; Shifa Javed was supported by Indian Council of Medical Research Junior Research Fellowships ICMR-JRF-2012/HRD-139(10056).

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Authors and Affiliations

  1. Molecular Pathology Laboratory, Department of Cytology & Gynec. Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, PIN-160023, India

    Shifa Javed & Radhika Srinivasan

  2. Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Shalmoli Bhattacharyya

  3. Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Rashmi Bagga

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  1. Shifa Javed
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  2. Shalmoli Bhattacharyya
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  3. Rashmi Bagga
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  4. Radhika Srinivasan
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Contributions

SJ conducted all experiments and manuscript writing; SB, RB and RS conceived the project, designed the study. All authors read and approved the final manuscript.

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Correspondence to Radhika Srinivasan.

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Javed, S., Bhattacharyya, S., Bagga, R. et al. Insulin growth factor-1 pathway in cervical carcinoma cancer stem cells. Mol Cell Biochem 473, 51–62 (2020). https://doi.org/10.1007/s11010-020-03807-6

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  • DOI: https://doi.org/10.1007/s11010-020-03807-6

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