title: Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells.
abstract: We have identified the presence of leupaxin (LPXN), which belongs to the paxillin extended family of focal adhesion-associated adaptor proteins, in prostate cancer cells. Previous studies have demonstrated that LPXN is a component of the podosomal signaling complex found in osteoclasts, where LPXN was found to associate with the protein tyrosine kinases Pyk2 and c-Src and the cytosolic protein tyrosine phosphatase-proline-, glutamate-, serine-, and threonine-rich sequence (PTP-PEST). In the current study, LPXN was detectable as a 50-kDa protein in PC-3 cells, a bone-derived metastatic prostate cancer cell line. In PC-3 cells, LPXN was also found to associate with Pyk2, c-Src, and PTP-PEST. A siRNA-mediated inhibition of LPXN resulted in decreased in vitro PC-3 cell migration. A recombinant adenoviral-mediated overexpression of LPXN resulted in an increased association of Pyk2 with LPXN, whereas a similar adenoviral-mediated overexpression of PTP-PEST resulted in decreased association of Pyk2 and c-Src with LPXN. The overexpression of LPXN in PC-3 cells resulted in increased migration, as assessed by in vitro Transwell migration assays. On the contrary, the overexpression of PTP-PEST in PC-3 cells resulted in decreased migration. The overexpression of LPXN resulted in increased activity of Rho GTPase, which was decreased in PTP-PEST-overexpressing cells. The increase in Rho GTPase activity following overexpression of LPXN was inhibited in the presence of Y27632, a selective inhibitor of Rho GTPase. In conclusion, our data demonstrate that LPXN forms a signaling complex with Pyk2, c-Src, and PTP-PEST to regulate migration of prostate cancer cells.
authors.affiliation: Dept. of Biomedical Sciences, Dental School, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Surasri Nandan
authors.initials: SN
authors.lastname: Sahu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nunez
authors.forename: Guang
authors.initials: G
authors.lastname: Bai
authors.forename: Anandarup
authors.initials: A
authors.lastname: Gupta
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction; D019061:src-Family Kinases
chemical_list: D015815:Cell Adhesion Molecules; C112251:LPXN protein, human; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases; C000631346:CSK protein, human; C516738:PTPN12 protein, human; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D017027:Protein Tyrosine Phosphatases