Fatty acid-binding protein 5 (FABP5)-related signal transduction pathway in castration-resistant prostate cancer cells: a potential therapeutic target



Naeem, Abdulghani A, Abdulsamad, Saud A, Rudland, Philip S ORCID: 0000-0002-7491-0846, Malki, Mohammed I and Ke, Youqiang ORCID: 0000-0001-5341-8644
(2019) Fatty acid-binding protein 5 (FABP5)-related signal transduction pathway in castration-resistant prostate cancer cells: a potential therapeutic target. PRECISION CLINICAL MEDICINE, 2 (3). pp. 192-196.

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Abstract

In this short communication, a novel fatty acid-binding protein 5 (FABP5)-related signal transduction pathway in prostate cancer is reviewed. In castration-resistant prostate cancer (CRPC) cells, the FABP5-related signal transduction pathway plays an important role during transformation of the cancer cells from androgen-dependent state to androgen-independent state. The detailed route of this signal transduction pathway can be described as follows: when FABP5 expression is increased as the increasing malignancy, excessive amounts of fatty acids from intra- and extra-cellular sources are transported into the nucleus of the cancer cells where they act as signalling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ). The phosphorylated or biologically activated PPARγ then modulates the expression of its downstream target regulatory genes to trigger a series of molecular events that eventually lead to enhanced tumour expansion and aggressiveness caused by an overgrowth of the cancer cells with a reduced apoptosis and an increased angiogenesis. Suppressing the FABP5-related pathway via RNA interference against FABP5 has produced a 63-fold reduction in the average size of the tumours developed from CRPC cells in nude mice, a seven-fold reduction of tumour incidence, and a 100% reduction of metastasis rate. Experimental treatments of CRPC with novel FABP5 inhibitors have successfully inhibited the malignant progression of CRPC cells both <i>in vitro</i> and in nude mouse. These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.

Item Type: Article
Uncontrolled Keywords: FABP5, CRPC, fatty acids, PPAR gamma, tumorigenicity, metastasis
Depositing User: Symplectic Admin
Date Deposited: 10 Sep 2019 12:35
Last Modified: 19 Jan 2023 00:27
DOI: 10.1093/pcmedi/pbz015
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3054122