Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer

Abstract

Clinical management of breast cancer (BC) metastasis remains an unmet need as it accounts for 90% of BC-associated mortality. Although the luminal subtype, which represents >70% of BC cases, is generally associated with a favorable outcome, it is susceptible to metastatic relapse as late as 15 years after treatment discontinuation. Seeking therapeutic approaches as well as screening tools to properly identify those patients with a higher risk of recurrence is therefore essential. Here, we report that the lipid-degrading enzyme fatty acid amide hydrolase (FAAH) is a predictor of long-term survival in patients with luminal BC, and that it blocks tumor progression and lung metastasis in cell and mouse models of BC. Together, our findings highlight the potential of FAAH as a biomarker with prognostic value in luminal BC and as a therapeutic target in metastatic disease.

Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation

“…The evidence gathered in this study reveals the profound importance of FAAH in the differentiation dynamics of MECs in the adult mammary gland, and raises potentially important implications for the pathogenesis of breast cancer. Recent work from our lab established that FAAH genetic inactivation in the MMTV-neu transgenic mouse model preceded the formation of highly proliferative, more aggressive tumors [ 27 ]. Here, we demonstrated that mammary glands from FAAH −/− mice show an expanded population of alveolar progenitors, which are the likely target for transformation in the MMTV-neu model [ 28 ].…”

A prognostic signature of fatty acid metabolism‐related genes for predicting survival of gastric cancer patients

“…[33,34] The biological roles of FAAH have been reported in the context of tumorigenicity of multiple cancers. [35,36] It has been demonstrated that FAAH was highly expressed in prostate cancer tissues and cell lines, and its knockdown was sufficient to inhibit the invasive ability of cancer cells. [37] Similarly, Ravi et al [38] reported that FAAH could enhance the tumorigenic and invasive effect in lung cancer by activating EGF/ EGFR signaling pathway.…”

Cannabis and cancer: unveiling the potential of a green ally in breast, colorectal, and prostate cancer

“…As well, it was stated that endogenous CB1 agonists as Anandamide, oleamide, and 2-Arachidonoylglycerol (works as CB1 and CB2 agonist) have an antiproliferative effect (Coelho et al 2023 ). Moreover, arvanil (which is a synthetic CB1 agonist) also inhibits cell proliferation (Tundidor et al 2023 ). Phytocannabinoids compounds were also tested in a study to investigate their abilities in inhibiting BC growth.…”