2. Academic Validation
  3. FAM98A promotes resistance to 5-fluorouracil in colorectal cancer by suppressing ferroptosis

FAM98A promotes resistance to 5-fluorouracil in colorectal cancer by suppressing ferroptosis

  • Arch Biochem Biophys. 2022 Jun 15;722:109216. doi: 10.1016/j.abb.2022.109216.
Zhanke He 1,  Junbo Yang 2,  Chuyang Sui 1,  Penghao Zhang 1,  Ting Wang 1,  Tingyu Mou 1,  Kai Sun 1,  Yanan Wang 1,  Zhijun Xu 1,  Guoxin Li 3,  Haijun Deng 4,  Jiaolong Shi 5,  Baoxiong Zhuang 6
Affiliations

Affiliations

  • 1 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 2 Department of Gastrointestinal Surgery, The Second Affiliated Hospital School of Medicine, Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen, China.
  • 3 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: gzliguoxin@163.com.
  • 4 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: navyd999@163.com.
  • 5 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: shijiaolong10@smu.edu.cn.
  • 6 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: 18820095121@163.com.
PMID: 35421356 DOI: 10.1016/j.abb.2022.109216
Abstract

Background: FAM98A is a microtubule-associated protein involved in cell proliferation and migration, and is frequently dysregulated in epithelial cancers. But its role in the development of colorectal Cancer (CRC) Cancer remains unknown.

Methods: Immunohistochemical analysis was performed to examine the expression of FAM98A in CRC samples. We also investigated the effects of abnormal expression on the biological behavior of colorectal Cancer cells both in vitro and in vivo. Immunoblotting and immunoprecipitation were used to screen FAM98A-related signalling pathways and downstream factors.

Results: FAM98A was upregulated in CRC tissues and CRC cell lines. Overexpression of FAM98A promoted cell proliferation and recovered 5-FU suppressed CRC cell proliferation both in vitro and in vivo. In addition, the Enhanced expression of FAM98A inhibited Ferroptosis in CRC cells by activating the translation of xCT in stress granules (SGs). Furthermore, we identified that metformin could reverse FAM98A-mediated 5-FU resistance in CRC cells.

Conclusions: Our results for the first time indicate that FAM98A plays a critical role in promoting CRC progression, which provides a novel target for clinical drug resistance of colorectal Cancer. And metformin may sensitize 5-FU in the treatment of colorectal Cancer.

Keywords

5-FU; Colorectal cancer; FAM98A; Ferroptosis.

Figures
Products