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

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.

CDK10 suppresses metastasis of lung adenocarcinoma through inhibition of the ETS2/c‐Raf/p‐MEK/p‐ERK signaling loop

“…It was determined that downregulation of CDK10 in LUAD was associated with metastasis of tumor and poor prognosis of patients. CDK10 has been documented to play dual roles in tumorigenesis, both as a candidate tumor suppressor in hepatocellular carcinoma, biliary tract cancers and gastric cancer, and as a potential oncogene in colorectal cancer 32 . In spite of the previous findings on breast cancer and biliary tract cancer, which disclosed that the downregulation of CDK10 correlated with lymph node metastasis and poor outcome, this was the first report that CDK10 functioned as an essential suppressor of metastasis in LUAD 21,33 .…”

“…CDK10 has been documented to play dual roles in tumorigenesis, both as a candidate tumor suppressor in hepatocellular carcinoma, biliary tract cancers and gastric cancer, and as a potential oncogene in colorectal cancer. 32 In spite of the previous findings on breast cancer and biliary tract cancer, which disclosed that the downregulation of CDK10 correlated with lymph node metastasis and poor outcome, this was the first report that CDK10 functioned as an essential suppressor of metastasis in LUAD. 21,33 The distinct findings in various types of malignancies suggest that CDK10 plays multifaceted roles in carcinogenesis dependent on the context of the intracellular signal network and the interacting partners available for CDK10.…”

Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury

“…CDK10, an essential regulator of the cell cycle, is essentially involved in regulating cell proliferation. Previous studies have highlighted the dual roles of CDK10 that can function as tumor suppressor or oncogene in cancers [ 55 – 57 ]. Lower level of CDK10 was associated with resistance to endocrine therapy in breast cancer patients [ 58 ].…”

Biomarker discovery with quantum neural networks: a case-study in CTLA4-activation pathways

“…Cyclin-dependent kinase 10 (CDK10) is a serine/threonine kinase related to CDC2 and plays a crucial role in various cellular processes such as cell proliferation, regulation of transcription, and cell cycle regulation. CDK10 has been identified as a candidate tumor suppressor in hepatocellular carcinoma, biliary tract cancers, and gastric cancer, but as a candidate oncogene in colorectal cancer (CRC) [6]. A study on CDK10's role in colorectal cancer revealed that it enhances cell growth, reduces chemosensitivity, and inhibits apoptosis by increasing the expression of BCL-2 [80].…”