2022 World Conference on Lung Cancer (ePosters)-EP16.04-030. Cancer-Associated Fibroblasts Attenuate DNA Damage Repair by Promoting Glycolysis in Non-small Cell Lung Cancer

EP16.04-030. Cancer-Associated Fibroblasts Attenuate DNA Damage Repair by Promoting Glycolysis in Non-small Cell Lung Cancer

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A recent study investigated the role of cancer-associated fibroblasts (CAFs) in the DNA damage response of non-small cell lung cancer (NSCLC) cells and the mechanisms involved. CAFs are abundant in the tumor microenvironment and can affect the response to radiotherapy in NSCLC patients. The study involved the establishment of CAFs and normal fibroblasts (NFs) from tumor and normal lung tissues respectively. The researchers found that CAFs attenuated DNA damage induced by irradiation and increased the expression of DNA damage repair proteins in NSCLC cells. CAFs also induced cell cycle arrest in the radioresistant S phase of NSCLC cells. Additionally, when co-cultured with CAFs, NSCLC cells showed an increase in glycolysis, characterized by accelerated glucose uptake and lactate secretion. The researchers found that CAFs up-regulated and stabilized c-myc, which initiated the transcription of HK2 kinase, a critical enzyme in glycolysis, through activation of the Wnt/β-catenin pathway. Inhibition of glycolysis attenuated the DNA damage response of NSCLC cells regulated by CAFs. The study also found that CAFs-secreted midkine was responsible for promoting glycolysis in NSCLC cells through activation of the Wnt/β-catenin pathway. Inhibition of CAFs-promoted glycolysis improved the radiosensitivity of NSCLC xenograft tumors in vivo. These findings contribute to understanding the role of CAFs in the DNA damage response of NSCLC cells and could provide insights into overcoming radioresistance in NSCLC treatment.

Asset Subtitle

Hongfang Zhang

Meta Tag

Speaker Hongfang Zhang

Topic Tumour Biology and Biomarkers - Tumour Biology & Preclinical Studies

Keywords

cancer-associated fibroblasts

DNA damage response

non-small cell lung cancer

tumor microenvironment

radiotherapy

fibroblasts

glycolysis

Wnt/β-catenin pathway

radiosensitivity

radioresistance