YAP Promotes Chemoresistance to 5-FU in Colorectal Cancer Through MTOR/GLUT3 Axis

Overview

Journal J Cancer

Specialty Oncology

Date 2024 Dec 13

PMID 39668819

Authors

Qixuan Xu

Zhesi Jin

Zhen Yuan

Zhiyuan Yu

Jingwang Gao

Ruiyang Zhao

Hanghang Li

Huiguang Ren

Bo Cao

Bo Wei

Linhua Jiang

Affiliations

Soon will be listed here.

Abstract

Although chemoresistance constitutes a significant barrier to the effectiveness of chemotherapy in colorectal cancer (CRC), its precise mechanisms remain unclear. YAP functions as an oncogene in various malignancies. However, the relationship between YAP and chemoresistance in CRC needs clarification. The expression level of YAP in CRC tissues was assessed through immunohistochemistry (IHC), and the impact of YAP on CRC cell chemoresistance was evaluated using the Cell Counting Kit-8, EdU, and flow cytometry assays. Meanwhile, tumor proliferation was assessed by analyzing the expression of PCNA and Ki-67 in subcutaneous tumors via IHC. In addition, the TUNEL assay was employed to evaluate tumor apoptosis levels and western blot was utilized to detect the mTOR/GLUT3 pathway-related protein expression to provide insights into the underlying mechanism. YAP was highly expressed in CRC tissues and correlated with patient prognosis and clinicopathological features. Bioinformatic analysis based on the TCGA database revealed that YAP was associated with DNA replication, glycolysis, and the mTOR pathway. Meanwhile, YAP could enhance chemoresistance and glycolysis in CRC cells both and . Additional mechanistic experiments unveiled that YAP promoted CRC cell chemoresistance via the mTOR/GLUT3 axis. This study validated the role of YAP as an oncogene in CRC, as it promoted chemoresistance through the mTOR/GLUT3 axis. These results suggested YAP as a potential target for promoting the efficacy of chemotherapy in patients with CRC.

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