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

## TL;DR

FAM65A overexpression promotes colorectal cancer progression by activating Ras/ERK/RSK signaling and could serve as a prognostic biomarker.

## Contribution

FAM65A is identified as a novel independent prognostic marker and driver of CRC progression via Ras/ERK/RSK signaling.

## Key findings

- FAM65A is overexpressed in CRC tissues and correlates with poor prognosis and pathological features.
- FAM65A promotes CRC cell proliferation and migration while reducing apoptosis in vitro and in vivo.
- FAM65A activates Ras/ERK/RSK signaling, and inhibiting this pathway counteracts its malignant effects.

## 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.

•FAM65A is overexpressed in CRC tissues and correlates with pathological features•FAM65A may serve as an independent prognostic biomarker for CRC patients•FAM65A expression promotes CRC malignant progression in vitro and in vivo•FAM65A binds to Ras and activates Ras/ERK/RSK signaling to mediate CRC progression

FAM65A is overexpressed in CRC tissues and correlates with pathological features

FAM65A may serve as an independent prognostic biomarker for CRC patients

FAM65A expression promotes CRC malignant progression in vitro and in vivo

FAM65A binds to Ras and activates Ras/ERK/RSK signaling to mediate CRC progression

Molecular biology; Cell biology; Cancer