Co-occurrence of aberrant hepatocyte growth factor (HGF)/MET proto-oncogene receptor tyrosine kinase (MET) and Wnt/β-catenin signaling pathways has been observed in advanced and metastatic prostate cancers.
Reduced prostate cancer risks were found for men engaging in medium (15.8-47.3 metabolic equivalent task [MET]-h/week) and high (>47.3 MET-h/week) physical activity levels, with the adjusted odds ratios being 0.52 (95% confidence interval = 0.35-0.77) and 0.27 (95% confidence interval = 0.14-0.49), respectively.
To further assess the biological role of MET in prostate cancer progression, we bred <i>H11</i><sup><i>Met/</i>+</sup><i>/Pten<sup>LoxP/LoxP</sup>:PBCre4</i> compound mice, in which transgenic <i>Met</i> expression and deletion of the tumor suppressor gene <i>Pten</i> occurred simultaneously only in prostatic epithelial cells.
This review outlines our current understanding of the contribution of EMT and its reversal to MET in prostate cancer progression and therapeutic resistance, and the impact of selected targeting of mechanisms of resistance via EMT towards a therapeutic benefit in patients with CRPC.
SOCS1, p53, MET and p21 protein expression were evaluated by immunohistochemical staining alongside the common prostate cancer-related markers Ki67, prostein and androgen receptor.
Prostate cancer (PCa) bone metastasis is uniquely associated with osteoblastic bone lesions and treatment with cabozantinib, a VEGFR-2 and MET inhibitor, leads to a reduction in number and/or intensity of lesions on bone scans.
MET-overexpressing human DU145 and PC3 PCa cell lines were stably transduced with SOCS1, and their growth, migration and invasion of collagen matrix were evaluated in vitro.
We identified 32 SNPs in five genes (TP63, ALDH1A1, WNT1, MET and EGFR) that were significantly associated with prostate cancer risk, of which six SNPs in three genes (TP63, ALDH1A1 and WNT1) and eight EGFR SNPs showed heterogeneity in susceptibility between these two racial groups.
Similarly, the expression of MET in AR(-) disease, whether due to AR inhibition or loss of AR signaling, suggests potential utility for MET inhibition in select patients with AR therapy resistance and in AR(-) prostate cancer.
The MET/Vascular Endothelial Growth Factor Receptor (VEGFR)-targeted Tyrosine Kinase Inhibitor Also Attenuates FMS-dependent Osteoclast Differentiation and Bone Destruction Induced by Prostate Cancer.
Pathologically, strong MET phosphorylation observed in specific architectures in prostate cancer, such as cribriform structures, ill-defined glands or solid patterns, suggested the significance of MET activation in promoting the architectural formation of prostate cancer.
MET amplification was found in 7 of 97 (7.2%) patients (4/27 renal [all clear cell], 1/18 urothelial, and 2/12 adrenocortical carcinoma), with MET mutation/variant in 3 of 54 (5.6%) (2/20 renal cell carcinoma [RCC] [1 clear cell and 1 papillary] and 1/16 prostate cancer).
These findings establish the importance of MET in prostate cancer progression but reveal potential limitations in the clinical use of MET inhibitors in late-stage prostate cancer.
In this study, using the prostate cancer cell line PC3 and the non-small lung cancer cell line A549, which have limited sensitivity to SAHA, we found that SAHA triggered MET and AKT phosphorylation at clinical concentrations. siRNA silencing of MET enhanced SAHA induced apoptosis in PC3 and A549 cells.
Stimulation of the prostate cancer cell line PC3 with IGF-1 induces a delayed phosphorylation of MET at multiple sites (indicative of full activation), reaching a maximum 18 hr after IGF-1 addition.
These findings provide a novel molecular mechanism of MET regulation in PCa and contribute to the increasing evidence that miR-34c has a key tumour suppressive role in PCa.
Importantly, NRP1 overexpression and c-MET activation were positively associated with progression and bone metastasis in human PCa specimens and xenograft tissues.
Molecular mechanism of adaphostin-mediated G1 arrest in prostate cancer (PC-3) cells: signaling events mediated by hepatocyte growth factor receptor, c-Met, and p38 MAPK pathways.