Signal Transduction Pathway in Maspin-Induced Tumor Suppression of Prostate Cancer

AbstractGlobally, prostate cancer ranks second in cancer burden of the men. It occurs more frequently in black men compared to white or Asian men. Usually, high rates exist for men aged 60 and above. In this review, we focus on the Wnt/β-catenin signal transduction pathway in prostate cancer since many studies have reported that β-catenin can function as an oncogene and is important in Wnt signaling. We also relate its expression to the androgen receptor and MMP-7 protein, both critical to prostate cancer pathogenesis. Some mutations in the androgen receptor also impact the androgen-β-catenin axis and hence, lead to the progression of prostate cancer. We have also reviewed MiRNAs that modulate this pathway in prostate cancer. Finally, we have summarized the impact of Wnt/β-catenin pathway proteins in the drug resistance of prostate cancer as it is a challenging facet of therapy development due to the complexity of signaling pathways interaction and cross-talk.

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

Precision Clinical Medicine ◽

10.1093/pcmedi/pbz015 ◽

2019 ◽

Vol 2 (3) ◽

pp. 192-196 ◽

Cited By ~ 2

Author(s):

Abdulghani A Naeem ◽

Saud A Abdulsamad ◽

Philip S Rudland ◽

Mohammed I Malki ◽

Youqiang Ke

Keyword(s):

Prostate Cancer ◽

Signal Transduction ◽

Cancer Cells ◽

Fatty Acid Binding Protein ◽

Signal Transduction Pathway ◽

Transduction Pathway ◽

Castration Resistant Prostate Cancer ◽

Fatty Acid Binding ◽

Castration Resistant ◽

Fold Reduction

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 in vitro and in nude mouse. These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.

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