Fatty acid binding protein 5 regulates docetaxel sensitivity in taxane-resistant prostate cancer cells

Hillowe, Andrew, Gordon, Chris, Wang, Liqun, Rizzo, Robert C, Trotman, Lloyd C, Ojima, Iwao, Bialkowska, Agnieszka, Kaczocha, Martin (2023) Fatty acid binding protein 5 regulates docetaxel sensitivity in taxane-resistant prostate cancer cells. PLoS One, 18 (10). e0292483. ISSN 1932-6203

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Abstract

Prostate cancer is a leading cause of cancer-related deaths in men in the United States. Although treatable when detected early, prostate cancer commonly transitions to an aggressive castration-resistant metastatic state. While taxane chemotherapeutics such as docetaxel are mainstay treatment options for prostate cancer, taxane resistance often develops. Fatty acid binding protein 5 (FABP5) is an intracellular lipid chaperone that is upregulated in advanced prostate cancer and is implicated as a key driver of its progression. The recent demonstration that FABP5 inhibitors produce synergistic inhibition of tumor growth when combined with taxane chemotherapeutics highlights the possibility that FABP5 may regulate other features of taxane function, including resistance. Employing taxane-resistant DU145-TXR cells and a combination of cytotoxicity, apoptosis, and cell cycle assays, our findings demonstrate that FABP5 knockdown sensitizes the cells to docetaxel. In contrast, docetaxel potency was unaffected by FABP5 knockdown in taxane-sensitive DU145 cells. Taxane-resistance in DU145-TXR cells stems from upregulation of the P-glycoprotein ATP binding cassette subfamily B member 1 (ABCB1). Expression analyses and functional assays confirmed that FABP5 knockdown in DU145-TXR cells markedly reduced ABCB1 expression and activity, respectively. Our study demonstrates a potential new function for FABP5 in regulating taxane sensitivity and the expression of a major P-glycoprotein efflux pump in prostate cancer cells.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > small molecules > ATP bioinformatics diseases & disorders > cancer diseases & disorders bioinformatics > genomics and proteomics diseases & disorders > neoplasms organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions diseases & disorders > cancer > cancer types > prostate cancer bioinformatics > genomics and proteomics > small molecules diseases & disorders > cancer > cancer types
CSHL Authors:	Trotman, Lloyd C.
Communities:	CSHL labs > Trotman lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2023
Date Deposited:	24 Oct 2023 13:19
Last Modified:	10 Jan 2024 19:18
PMCID:	PMC10553314
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41283

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