Pluripotency inducing Yamanaka factors: role in stemness and chemoresistance of liver cancer

ABSTRACT

Introduction: Liver cancer is a major cause of mortality and is characterized by the transformation of cells into an uncontrolled mass of tumor cells with many genetic and epigenetic changes, which lead to the development of tumors. A small subpopulation of cell population known as Cancer Stem Cells (CSCs) is responsible for cancer stemness and chemoresistance. Yamanaka factors [octamer-binding transcription factor 4 (OCT4), SRY (sex-determining region Y)-box 2 (SOX2), kruppel-like factor 4 (KLF4), and Myelocytomatosis (MYC); OSKM] are responsible for cancer cell stemness, chemoresistance, and recurrence.

Area covered: We cover recent discoveries and investigate the role of OSKM in inducing pluripotency and stem cell-like properties in various cancers with special emphasis on liver cancer. We review Yamanaka factors’ role in stemness and chemoresistance of liver cancer.

Expert opinion: In CSCs, including liver CSCs, the deregulation of various signaling pathways is one of the major reasons for stemness and drug resistance and is primarily due to OSKM. OSKM are responsible for tumor heterogeneity which renders targeting drug useless after a certain period. These factors can be exploited to understand the underlying mechanism of cancer stemness and resistance to chemotherapeutic drugs.

Graphical Abstract

KEYWORDS:

• Yamanaka factors
• stemness
• chemoresistance
• liver cancer

Article highlights

• Yamanaka factors (c-MYC, Klf4, SRY, OCT4) are highly expressed in embryonic stem cells and are responsible for inducing pluripotency in differentiated cells

• In cancer, Yamanaka factors are involved in maintaining tumor cell heterogeneity

• Their expressions are directly linked to the stemness features of cancer cells

• Cancer cell stemness increases the number of cancer Stem cells

• Cancer stem cells are responsible for cancer chemoresistance and recurrence

Acknowledgments

The authors are thankful to the Department of Zoology, AMU, Aligarh for providing the necessary facilities. HF expresses her sincere gratitude to UGC for MAN Fellowship, India, for financial support. HRS is thankful to the UGC and DST-SERB, New Delhi, for providing financial help.

Declaration of interest

No potential conflict of interest was reported by the author(s).

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by University Grants Commission [Grant no. F.30-377/2017(BSR)], DST-SERB (Grant no. EMR/20l7/001758), India.