PDLIM4 increases sphingolipid accumulation to promote cancer stem cell characteristics and chemotherapy resistance in colorectal cancer
9 affiliations
- 1Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 2Minimally Invasive Center for Hepatobiliary and Pancreatic Surgery, Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine, Zhuhai, China
- 3Department of Hepatobiliary, Pancreatic and Splenic surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 4Department of Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 5Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 6Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China
- 7Department of Human Anatomy, Histology and Embryology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
- 8Department of Obstetrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 9Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Abstract
The prognosis for advanced colorectal cancer (CRC) remains poor, and 5-fluorouracil (5-FU)-based chemotherapy is the primary treatment option. Understanding the mechanisms that limit the effectiveness of this therapy is therefore clinically important. However, the molecular drivers of acquired chemotherapy resistance in advanced CRC are not fully understood. Here we show that expression of PDZ-LIM domain-containing protein 4 (PDLIM4) is significantly upregulated following neoadjuvant chemotherapy in patients with advanced CRC, and that its expression level is closely associated with patient prognosis. PDLIM4 promotes acquired resistance to 5-FU by enhancing the stemness, anti-apoptotic capacity, and drug efflux of colorectal cancer stem cells. Mechanistically, PDLIM4 facilitates the accumulation of sphingolipids, particularly sphingomyelin, and regulates the PI3K/Akt signaling pathway. These findings identify PDLIM4 as a potential biomarker and therapeutic target for overcoming chemoresistance in advanced colorectal cancer, opening new avenues for future treatment strategies.
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BibTeX
@article{song2026pdlim4,
title = {{PDLIM4 increases sphingolipid accumulation to promote cancer stem cell characteristics and chemotherapy resistance in colorectal cancer}},
author = {Yingqiu Song and Zhiyong Xiong and Dagui Zhou and Ya-Han Ren and Qianhui Liu and Xu Lu and Jinyang Wang and Ziyan Zhu and Yongsheng Tang and Hao Li and Manqiu Kang and Ling Li and Xiaofeng Yang and Tiantian Wang and Changchang Jia and Jiafeng Fang},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10627-9},
url = {https://doi.org/10.1038/s42003-026-10627-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - PDLIM4 increases sphingolipid accumulation to promote cancer stem cell characteristics and chemotherapy resistance in colorectal cancer
AU - Yingqiu Song
AU - Zhiyong Xiong
AU - Dagui Zhou
AU - Ya-Han Ren
AU - Qianhui Liu
AU - Xu Lu
AU - Jinyang Wang
AU - Ziyan Zhu
AU - Yongsheng Tang
AU - Hao Li
AU - Manqiu Kang
AU - Ling Li
AU - Xiaofeng Yang
AU - Tiantian Wang
AU - Changchang Jia
AU - Jiafeng Fang
PY - 2026
DA - 2026/07/01
JO - Communications Biology
DO - 10.1038/s42003-026-10627-9
UR - https://doi.org/10.1038/s42003-026-10627-9
AB - The prognosis for advanced colorectal cancer (CRC) remains poor, and 5-fluorouracil (5-FU)-based chemotherapy is the primary treatment option. Understanding the mechanisms that limit the effectiveness of this therapy is therefore clinically important. However, the molecular drivers of acquired chemotherapy resistance in advanced CRC are not fully understood. Here we show that expression of PDZ-LIM domain-containing protein 4 (PDLIM4) is significantly upregulated following neoadjuvant chemotherapy in patients with advanced CRC, and that its expression level is closely associated with patient prognosis. PDLIM4 promotes acquired resistance to 5-FU by enhancing the stemness, anti-apoptotic capacity, and drug efflux of colorectal cancer stem cells. Mechanistically, PDLIM4 facilitates the accumulation of sphingolipids, particularly sphingomyelin, and regulates the PI3K/Akt signaling pathway. These findings identify PDLIM4 as a potential biomarker and therapeutic target for overcoming chemoresistance in advanced colorectal cancer, opening new avenues for future treatment strategies.
SN - 2399-3642
ER -