2. Academic Validation
  3. FAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling

FAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling

  • iScience. 2026 Jan 10;29(2):114662. doi: 10.1016/j.isci.2026.114662.
Yuqiu Ma 1 2 3,  Jie Yao 4,  Xinzhuang Shen 2,  Shuying Wang 2,  Gongli Tang 5,  Xiaowen Yang 2,  Yifei Li 3,  Yifang Sun 6,  Wenzhi Shen 2,  Xiaoyuan Zhang 2,  Yongming Huang 1
Affiliations

Affiliations

  • 1 Department of General Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining 272000, China.
  • 2 Key Laboratory of Precision Oncology in Universities of Shandong, Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
  • 3 Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
  • 4 Department of Oncology, Jining Hospital of Traditional Chinese Medicine, Jining 272000, China.
  • 5 Local Town Centre Health Centre of Difang, Pingyi County, Shandong Province 273306, China.
  • 6 Department of Ultrasound, Affiliated Hospital of Jining Medical University, Jining 272000, China.
PMID: 41660236 DOI: 10.1016/j.isci.2026.114662
Abstract

Research indicates that FAM65A is significantly involved in tumorigenesis. Nevertheless, the prognostic implications of FAM65A expression levels and its contribution to CRC malignant progression have yet to be elucidated. Here, we revealed that FAM65A is overexpressed in CRC tissues and is linked to various pathological indicators and patient prognosis. Importantly, COX regression analysis indicated that FAM65A may function as an independent prognostic marker. Furthermore, functional assays conducted in vitro demonstrated that FAM65A enhanced CRC cell proliferation and migration, alongside decreased Apoptosis. Mechanistically, we elucidated that FAM65A binds to Ras and activates the Ras/extracellular regulated protein kinases (ERK) signaling to mediate RSK activation contributes to CRC progression, treatment with the Ras Inhibitor Abd-7 or RSK inhibitor BRD7389 effectively countered the FAM65A-mediated enhancement of malignancy. Additionally, in vivo experiments indicated that FAM65A knockdown led to the inhibition of Ras/ERK/RSK activation and subsequently impeded CRC progression. Our study provides targets and strategies for the treatment of CRC.

Keywords

Cancer; Cell biology; Molecular biology.

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