Fatty acid synthase enhances colorectal cancer cell proliferation and metastasis via regulating AMPK/mTOR pathway

Onco Targets Ther. 2019 May 2:12:3339-3347. doi: 10.2147/OTT.S199369. eCollection 2019.

Abstract

Objective: In the present study, we aimed to investigate the potential role of fatty acid synthase (FASN) in the development and progression of colorectal cancer (CRC). Materials and methods: FASN levels were analyzed in human CRC tissues and adjacent normal tissues by Western blots and immunohistochemistry. Potential roles of FASN in regulating CRC cell proliferation and migration were examined by genetic manipulation in vitro. The molecular signaling was determined to understand the mechanisms of observed FASN effects. Results: FASN level was upregulated in CRC tissues and high expression of FASN was significantly associated with lymph node metastasis, TNM (Tumor, Node, Metastases) stage and poor prognosis in patients with CRC. Knockdown of FASN attenuated CRC cell proliferation and migration in vitro while FASN overexpression possessed the opposite effects. FASN regulated AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) pathway in CRC cells. Conclusion: FASN enhanced CRC cell proliferation and metastasis potentially through AMPK/mTOR pathway, indicating that FASN/AMPK/mTOR signaling axis may serve as a potential target for the treatment of CRC.

Keywords: AMPK/mTOR pathway; FASN; colorectal cancer; metastasis; proliferation.