The POU2F1-ALDOA Axis Promotes the Proliferation and Chemoresistance of Colon Cancer Cells by Enhancing Glycolysis and the Pentose Phosphate Pathway Activity

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2022 Jan 8

PMID 34997215

Citations 28

Authors

Jinguan Lin

Longzheng Xia

Linda Oyang

Jiaxin Liang

Shiming Tan

Nayiyuan Wu

Pin Yi

Qing Pan

Shan Rao

Yaqian Han

Yanyan Tang

Min Su

Xia Luo

Yiqing Yang

Xiaohui Chen

Lixia Yang

Yujuan Zhou

Qianjin Liao

Affiliations

Soon will be listed here.

Abstract

Cancer metabolic reprogramming enhances its malignant behaviors and drug resistance, which is regulated by POU domain transcription factors. This study explored the effect of POU domain class 2 transcription factor 1 (POU2F1) on metabolic reprogramming in colon cancer. The POU2F1 expression was analyzed in GEO dataset, TCGA cohorts and human colon cancer tissues by bioinformatics and immunohistochemistry. The effects of altered POU2F1 expression on proliferation, glucose metabolism and oxaliplatin sensitivity of colon cancer cells were tested. The impacts of POU2F1 on aldolase A (ALDOA) expression and malignant behaviors of colon cancer cells were examined. We found that up-regulated POU2F1 expression was associated with worse prognosis and oxaliplatin resistance in colon cancer. POU2F1 enhanced the proliferation, aerobic glycolysis and the pentose phosphate pathway (PPP) activity, but reduced oxidative stress and apoptosis in colon cancer cells, dependent on up-regulating ALDOA expression. Mechanistically, POU2F1 directly bound to the ALDOA promoter to enhance the ALDOA promoter activity in colon cancer cells. Moreover, activation of the POU2F1-ALDOA axis decreased the sensitivity to oxaliplatin in colon cancer cells. These data indicate that the POU2F1-ALDOA axis promotes the progression and oxaliplatin resistance by enhancing metabolic reprogramming in colon cancer. Our findings suggest that the POU2F1-ALDOA axis may be new therapeutic targets to overcome oxaliplatin resistance in colon cancer.

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