CDK10 in Gastrointestinal Cancers: Dual Roles as a Tumor Suppressor and Oncogene.

Isabella T. Tai,Zainab A. Bazzi

doi:10.3389/fonc.2021.655479

Abstract

Cyclin-dependent kinase 10 (CDK10) is a CDC2-related serine/threonine kinase involved in cellular processes including cell proliferation, transcription regulation and cell cycle regulation. CDK10 has been identified as both a candidate tumor suppressor in hepatocellular carcinoma, biliary tract cancers and gastric cancer, and a candidate oncogene in colorectal cancer (CRC). CDK10 has been shown to be specifically involved in modulating cancer cell proliferation, motility and chemosensitivity. Specifically, in CRC, it may represent a viable biomarker and target for chemoresistance. The development of therapeutics targeting CDK10 has been hindered by lack a specific small molecule inhibitor for CDK10 kinase activity, due to a lack of a high throughput screening assay. Recently, a novel CDK10 kinase activity assay has been developed, which will aid in the development of small molecule inhibitors targeting CDK10 activity. Discovery of a small molecular inhibitor for CDK10 would facilitate further exploration of its biological functions and affirm its candidacy as a therapeutic target, specifically for CRC.

Highlights

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that play a critical role in regulating cellular processes, including cell division and cell death [1]
Further research is warranted to delineate the mechanism by which Cyclin-dependent kinase 10 (CDK10) regulates c-Raf levels in gastrointestinal cancers and how that results in cell cycle arrest
CDK10 is involved in cell proliferation, cell motility, and plays an important role in chemosensitivity and chemoresistance

Summary

Introduction

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that play a critical role in regulating cellular processes, including cell division and cell death [1]. Using a yeast interaction trap, CDK10 was shown to bind to transcription factor ETS2, both in vitro and in vivo, using human embryonic kidney 293 cells (Figure 1) [65]. Cyclin M, has yet to be shown to be a CDK10 binding partner in gastrointestinal and hepatobiliary cancers. Further studies are warranted to assess these as candidate binding partners for CDK10 in humans, and cancers involving the gastrointestinal tract and hepatobiliary system.

Results

Conclusion