Predictive value of PAK6 and PSMB4 expression in patients with localized prostate cancer treated with dose-escalation radiation therapy and androgen deprivation therapy

Zapatero, A.; Morente, Manuel; Nieto, Santiago; Vidales, C. Martín de; López, Consuelo; Adrados, Magdalena; Arellano, R.; Artiga, María J.; Garcı́a-Vicente, Feliciano; Herranz, Luis Miguel de la Cruz; Leaman, O.

doi:10.1016/j.urolonc.2014.05.004

Cited by 8 publications

(4 citation statements)

References 12 publications

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“…Moreover, PAK6 can interact with the androgen receptor and translocate to the nucleus, and plays a role in the regulation of gene transcription (20,21). The deregulated expression of PAK6 has been identified in several cancers, including prostate cancer, hepatocellular carcinoma and thyroid cancer (22)(23)(24). In the present study, we identified, to the best of our knowledge, for the first time PAK6 is a direct target gene of miR-429 in colon cancer cells and that PAK6, upregulated in colon cancer cells, was negatively regulated by miR-429.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling

et al. 2015

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MicroRNAs (miRs), a class of non-coding RNAs 18-25 nucleotides in length, can lead to mRNA degradation or inhibit protein translation by directly binding to the 3'-untranslational region (UTR) of their target mRNAs. The deregulation of miR-429 has been suggested to be involved in the development and progression of colon cancer. However, the detailed molecular mechanism involved remains to be determined. The aim of the present study was to investigate the role of miR-429 in the regulation of migration and invasion of colon cancer cells using RT-qPCR and western blotting. The results showed that the expression of miR-429 was reduced in colon cancer cell lines, when compared to a normal colon epithelial cell line. Treatment with DNA demethylation agent 5-aza-2'-deoxycytidine and histone deacetylase inhibitor phenylbutyrate (PBA), or transfection with the pre-miR-429 lentivirus plasmid led to the upregulation of miR-429 expression, as well as inhibition of migration and invasion in colon cancer cells. Investigation of the molecular mechanism showed that PAK6 was a novel target of miR-429, and the expression of PAK6 was upregulated in colon cancer tissues and cell lines, and was negatively regulated by miR-429 in colon cancer cells. Moreover, the cofilin signaling acted as a downstream effector of miR-429 in colon cancer cells. In conclusion, the results of the present study suggested that miR-429 inhibits the migration and invasion of colon cancer cells, partly at least, by mediating the expression of PAK6, as well as the activity of cofilin signaling. Therefore, miR-429 is as a potential molecular target for the treatment of colon cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling

et al. 2015

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“…In NIH/3T3 cells, the expression of PSMB4 promotes both anchorage-independent growth and tumorigenesis [12]. Furthermore, the upregulated expression of PSMB4 is positively correlated with poorer recurrence-free survival in breast cancer, metastasis-free survival in prostate cancer and lower overall survival in ovarian and prostate cancer [11, 12]. In a recent study, PSMB4 has also been identified as a survival gene required for the proliferation of human glioblastoma cells [13].…”

Section: Discussionmentioning

confidence: 99%

“…PSMB4 is highly expressed in multiple cancer types, such as myeloma [8], hepatocellular carcinoma [9], ovarian cancer [10] and prostate cancer [11]. In epithelial ovarian cancer, PSMB4 expression is higher than that in normal ovary tissues and is positively related to poor prognosis and clinical pathologic variables [10].…”

Section: Introductionmentioning

confidence: 99%

Interference with PSMB4 Expression Exerts an Anti-Tumor Effect by Decreasing the Invasion and Proliferation of Human Glioblastoma Cells

Cheng

Tsai

Sung

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis. Proteasome subunit beta type-4 (PSMB4) is an essential subunit that contributes to the assembly of the 20S proteasome complex. However, the role of PSMB4 in glioblastomas remains to be clarified. The aim of this study was to investigate the role of PSMB4 in GBM tumor progression. Methods: We first analyzed the PSMB4 protein and mRNA expression in 80 clinical brain specimens and 77 datasets from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Next, we inhibited the PSMB4 expression by siRNA in cellular and animal models to explore PSMB4’s underlying mechanisms. The cell survival after siPSMB4 transfection was assayed by MTT assay. Annexin V and propidium iodide staining was used to monitor the apoptosis by flow cytometric analysis. Moreover, the migration and invasion were evaluated by wound healing and Transwell assays. The expression of migration-related and invasion-related proteins after PSMB4 inhibition was detected by Western blotting. In addition, an orthotropic xenograft mouse model was used to assay the effect of PSMB4 knockdown in the in vivo study. Results: Basis on the results of bioinformatics study, glioma patients with higher PSMB4 expression had a shorter survival time than those with lower PSMB4 expression. The staining of clinical brain tissues showed elevated PSMB4 expression in GBM tissues compared with normal brain tissues. The PSMB4 inhibition decreased proliferation, migration and invasion abilities in human GBM cells. Downregulated PSMB4 resulted in cell cycle arrest and apoptosis in vitro. In an orthotropic xenograft mouse model, the glioma tumors progression was reduced when PSMB4 was down-regulated. The decreased PSMB4 enhanced the anti-tumor effect of temozolomide (TMZ) on tumor growth. In addition, the absence of PSMB4 decreased the expression of phosphorylated focal adhesion kinase and matrix metallopeptidase 9 in vivo. Conclusion: PSMB4 inhibition in combination with TMZ may exert an anti-tumor effect by decreasing cell proliferation and invasion as well as by promoting apoptosis in human glioblastoma cells. This research may improve the therapeutic efficacy of glioblastoma treatment.

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“…The underlying mechanisms by which PAK6 mediates radiation therapy responses involves changes in cell cycle distribution, altered BAD phosphorylation, and impaired DNA double-strand break repair (Zhang et al, 2010). In addition, PAK6 expression is significantly associated with Proteasome beta-4 subunit (PSMB4) (Zapatero et al, 2014). The over-expression of PSMB4 and its role in proteasome mediated survival inhibition has been demonstrated in several metastatic and primary solid tumors (Liu et al, 2016).…”

Section: Prostate Cancermentioning

confidence: 99%

PAK6: a potential anti-cancer target

Gong

Pei

2020

Braz. J. Pharm. Sci.

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p21-activated kinase 6 (PAK6) is a member of the PAK family of serine/threonine kinases that are known effectors of Rho GTPases Cdc42 and Rac. PAKs regulate a large number of complex cellular mechanisms, including cell motility, morphology, and tumor development. PAK6, initially cloned as an interacting partner of the androgen receptor (AR), is associated with an array of cellular processes implicated in tumor progression. However, the full biological implications of PAK6 activity during cancer remain poorly understood. In this review, we assess our current understanding of the physiological roles of classical PAK6 functionality in mammals, in addition to its emerging role in tumorigenesis.

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Predictive value of PAK6 and PSMB4 expression in patients with localized prostate cancer treated with dose-escalation radiation therapy and androgen deprivation therapy

Cited by 8 publications

References 12 publications

MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling

MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling

Interference with PSMB4 Expression Exerts an Anti-Tumor Effect by Decreasing the Invasion and Proliferation of Human Glioblastoma Cells

PAK6: a potential anti-cancer target

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