title: Suppression of LASP-1 attenuates the carcinogenesis of prostatic cancer cell lines: Key role of the NF-κB pathway.
abstract: Prostate cancer (PCa) is one of the most frequently diagnosed cancers among males worldwide and causes a considerable number of deaths each year. One of the newly explored targets for the development of therapies against PCa is LIM and SH3 protein 1 (LASP-1). In the present study, the function of LASP-1 in the oncogenesis and metastasis of PCa was investigated using a series of in vitro experiments. Moreover, the mechanism through which LASP-1 exerted its effect on the carcinogenesis of PCa was also explored. The expression levels of LASP-1 in clinical PCa specimens were determined both at the mRNA and protein levels. Afterwards, the activity of LASP-1 in human PCa cell lines PC3 and DU145 was inhibited using a short hairpin RNA (shRNA) interfering method. The effects of LASP-1 knockdown on the cell growth, apoptosis, cell cycle distribution, migration and invasion were assessed. It was demonstrated that the expression of LASP-1 was significantly higher in the clinical PCa tissues than the level in the corresponding para-carcinoma tissues. Following the knockdown of the LASP-1 gene in human PCa cell lines, the viability, migration and invasion of the cancer cells were decreased. It was also demonstrated that the change in the cell viability and motile ability were associated with an induction of cell apoptosis and G1 phase cell cycle arrest. Based on the results of the detection of the expression of NF-κB-related factors, it was indicated that LASP-1 may affect the carcinogenesis of PCa through a NF-κB inhibition-dependent manner. Although the detailed explanation of the mechanism of LASP-1 in the carcinogenesis of PCa requires further elucidation, the present study highlights the potential of LASP-1 as a promising therapeutic target to ameliorate the oncogenesis and metastasis of PCa.
authors.affiliation: Department of Urology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Urology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Urology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Shao
authors.affiliation: Shandong University School of Life Sciences, Jinan, Shandong 250100, P.R. China.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Shandong University School of Life Sciences, Jinan, Shandong 250100, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Urology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Shengtian
authors.initials: S
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering