title: Clinicopathological signature of p21-activated kinase 1 in prostate cancer and its regulation of proliferation and autophagy via the mTOR signaling pathway.
abstract: Prostate cancer (PCa) is one of the most common malignant tumors in men. The etiology and pathogenesis of PCa remain unclear. P21-activated kinase 1 (PAK1) is a member of a family of serine/threonine kinases and regulates cell growth and contributes to tumor invasion and metastasis. However, the association of PAK1 with PCa tumorigenesis and in particular with cell autophagy remains unknown. We found that the positive expression of PAK1 was significantly increased in PCa patients compared with BPH patients (P < 0.05). The expression of PAK1, p-PAK1 and LC3B1 in DU145 was increased by the activator of mTOR MYH1485. The expression of PAK1, p-PAK1, mTOR and Beclin1 decreased in PAK1-shRNA expressing DU145 cell. Knocking down of PAK1 inhibited DU145 cell growth, invasion and migration in vitro, and inhibited tumor growth in vivo. Our study demonstrated that PAK1 is upregulated in PCa and regulated by the mTOR signaling pathway and contributes to tumor autophagy. Thus, PAK1 may be a potential tumor marker and therapeutic target of PCa.
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Zhanyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Guojin
authors.initials: G
authors.lastname: Jia
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Jikai
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Luo
authors.affiliation: Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D001343:Autophagy; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D059467:Transcriptome; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071186:Beclin-1; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C546842:MTOR protein, human; C515903:PAK1 protein, human; D058570:TOR Serine-Threonine Kinases; D054462:p21-Activated Kinases
keywords: MYH1485; PAK1; mTOR signaling; prostate cancer; rapamycin