APOA5 Alleviates Reactive Oxygen Species to Promote Oxaliplatin Resistance in PIK3CA-mutated Colorectal Cancer

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2024 Jun 7

PMID 38848145

Authors

Yu-Lin Liu

Zhuo Xiang

Bo-Ya Zhang

Yu-Wei Zou

Gui-Lai Chen

Li Yin

Yan-Long Shi

Li-Li Xu

Jingwang Bi

Qiang Wang

Affiliations

Soon will be listed here.

Abstract

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment and . Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.

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