Differential expressions of integrin‑linked kinase, β‑parvin and cofilin 1 in high‑fat diet induced prostate cancer progression in a transgenic mouse model

Abstract

High-fat diet induced obesity was associated with more aggressive prostate cancer. Recent research has demonstrated that integrin-linked kinase (ILK), β-parvin and downstream cofilin 1 jointly affected cancer progression. Meanwhile, these proteins were also involved in energy metabolism. Therefore, the present study was conducted to investigate the potential function of ILK, β-parvin and cofilin 1 in the high-fat diet-induced progression of prostate cancer. Transgenic mice with prostate cancer were employed, fed with different diets and sacrificed at 20 and 28 weeks. Tumor differentiation, extracapsular extension and metastasis were compared between the groups. Expression levels of ILK, β-parvin and cofilin 1 in prostate were evaluated by immunohistochemical analysis and determined by an immunoreactivity score. Public databases were applied for analysis and validation. It was detected that high-fat diet feeding promoted cancer progression in transgenic mice with prostate cancer, with increased expressions of β-parvin (P=0.038) and cofilin 1 (P=0.018). Higher expressions of ILK, β-parvin and cofilin 1 were also associated with poorer cancer differentiation. Additionally, higher mRNA levels of CFL1 were correlated with a worse disease-free survival in patients of certain subgroups from The Cancer Genome Atlas database. Further studies were warranted in discussing the potential roles of ILK, β-parvin and cofilin 1 in high-fat diet feeding induced progression of prostate cancer.

PARVB promotes malignant melanoma progression and is enhanced by hypoxic conditions

“…PARVB, an actin-binding protein, is intricately involved in cell-extracellular matrix (ECM) adhesion and plays pivotal roles in modulating cell survival and morphology. Although its abundant expression in organs such as the spleen, kidneys, heart, and skeletal muscles has been documented and its regulatory influence in healthy cells partly clarified [ 24 , 25 ], its expression pattern in cancer contexts remains enigmatic [ 17 , [26] , [27] , [28] , [29] ]. Some studies reveal diminished PARVB expression in breast cancer, suggesting a tumor-suppressive role [ 30 , 31 ].…”

Downregulation of PARVA promotes metastasis by modulating integrin-linked kinase activity and regulating MAPK/ERK and MLC2 signaling in prostate cancer

“…Dysregulation of ILK signaling was found in several hormonal tumors including breast, ovary and prostate (37). Hu et al reported that ILK overexpression was associated with poorly-differentiated PCa (38). Aberrant ERG translocations activates ILKmediated EMT progression in approximately half of PCa (39).…”

Research Evidence on High-Fat Diet-Induced Prostate Cancer Development and Progression

“…TRAMP mice develop prostatic intraepithelial neoplasia (PIN) by the time they are 6 weeks old; this progresses to high-grade PIN by the age of 12 weeks and poorly differentiated and invasive adenocarcinoma by the age of 24 weeks, with nearly 100% penetrance [61]. The impact of a HFD on the growth of TRAMP mouse tumors had been frequently evaluated [25,31,39,41,42,43,57,62]. Accordingly, Llaverias et al showed that mice consuming a Western-type diet enriched in both fat and cholesterol had higher prostate tumor incidence and greater tumor burden compared to those fed a control chow diet [25].…”

“…Moreover, HFD-fed TRAMP mice had significantly higher tumor incidence at 20 weeks, as compared to the normal diet group (78.57% and 35.71%, p = 0.022, respectively) [43]. The same group also showed that HFD-fed mice suffered higher rates of extracapsular extension (20 weeks, 16.7% vs. 8.3%; 28 weeks, 66.7% vs. 50.0%, respectively) and distant metastasis (e.g., retroperitoneal lymph nodes or lung metastasis) (28 weeks, 41.7% vs. 25.0%, respectively) [62]. Bonorden et al conducted a unique study involving the largest number of mice ( n = 25 each) to assess the direct effect of diet and body weight on prostate tumors.…”