3050 - CDK15 Promotes Esophageal Squamous Cell Carcinoma Progression by Phosphorylating HK<sub>2</sub> and Regulating Glycolysis

05:00pm - 06:00pm PT

Hall F

Screen: 15

POSTER

Presenter(s)

Hong Ge, MD - Henan Cancer Hospital, Zhengzhou, Henan

H. Ge¹, and N. Wang²; ¹Department of Radiation Oncology, Henan Cancer Hospital, Zhengzhou, Henan, China, ²The affiliated Cancer Hospital of Zhengzhou University, Zheng Zhou, China

Purpose/Objective(s):

Esophageal squamous cell carcinoma (ESCC) is the predominant pathological type of esophageal cancer in China, accounting for approximately 90% of all newly diagnosed cases. However, few effective therapeutic targets exist for ESCC patients. This study aims to investigate the role of CDK15 in ESCC progression and its potential as a therapeutic target.

Materials/Methods:

The expression of CDK15 in esophageal cancer cell lines was assessed by Western blot. Meanwhile, the expression of CDK15 in patients’ tumor tissues was compared with that in adjacent normal tissues using qRT-PCR. Stable CDK15 knockdown was established in KYSE150 and KYSE410 cell lines, and overexpressed in KYSE30 and KYSE510 cell lines. The effect of CDK15 on ESCC cell proliferation was evaluated through MTT, soft agar and plate colony formation assays. Pull-down/MS analysis was conducted to identify CDK15-interacting proteins. The binding between CDK15 and HK2 was examined by Co-immunoprecipitation (Co-IP). Additionally, the effect of CDK15 knockdown on HK2 activity and glucose uptake was investigated.

Results:

CDK15 is significantly overexpressed in both ESCC protein samples and tumor tissues, compared to adjacent normal tissues. CDK15 knockdown significantly inhibits ESCC cell proliferation, migration and colony formation, while its overexpression enhances these processes. The results of pull-down/MS and Co-IP show that CDK15 interacts with HK2 and promotes ESCC proliferation by regulating glycolysis. CDK15 knockdown reduces HK2 activity and glucose uptake, thereby limiting tumor energy intake and inhibiting tumor growth.

Conclusion:

Our data reveal the pivotal role of CDK15 in ESCC progression and demonstrate CDK15 promotes ESCC tumorigenesis by interacting with HK2. Hence, the CDK15-HK2 axis may serve as a novel therapeutic target for ESCC.