biostudies-literatureUnknown29(2)Ma YResearch 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 <i>FAM65A</i> is overexpressed in CRC tissues and is linked to various pathological indicators and patient prognosis. Importantly, Cox regression analysis indicated that <i>FAM65A</i> may function as an independent prognostic marker. Furthermore, functional assays conducted <i>in vitro</i> 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 ciScience114662https://www.ebi.ac.uk/biostudies/studies/S-EPMC12874459biostudies-literatureFAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling.PMC12874459Yang XYao JLi YHuang YWang SZhang XMa YTang GShen XSun YShen WfalseFAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling.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 <i>FAM65A</i> is overexpressed in CRC tissues and is linked to various pathological indicators and patient prognosis. Importantly, Cox regression analysis indicated that <i>FAM65A</i> may function as an independent prognostic marker. Furthermore, functional assays conducted <i>in vitro</i> 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 c2026-01-01T00:00:00Z2026 Feb2026-07-15T06:40:41.219Z2026-06-30T03:22:38.263ZS-EPMC128744594166023610.1016/j.isci.2026.114662