title: Expression of the adaptor protein Tks5 in human cancer: prognostic potential.
abstract: Tks5 (tyrosine kinase substrate with 5 SH3 domains) is an adaptor protein which cooperates with Src tyrosine kinase to promote the formation of protease-enriched, actin-based projections known as invadopodia, which are utilized by invasive cancer cells to degrade the extracellular matrix (ECM). We previously identified a Src-Tks5-Nck pathway which promotes invadopodium formation and ECM proteolysis in melanoma and breast cancer cells. We therefore sought to investigate the significance of Tks5 expression in human cancers. This was undertaken retrospectively through an immunohistochemical evaluation in tissue microarray cores and through data mining of the public database, Oncomine. Here we showed that Tks5 was expressed at higher levels in the microarray cores of breast, colon, lung and prostate cancer tissues compared to the levels in normal tissues. Importantly, mining of Oncomine datasets revealed a strong correlation between Tks5 mRNA overexpression in a number of cancers with increased metastatic events and a poorer prognosis. Collectively, these findings suggest a clinical association of Tks5 expression in human cancers. It identifies the importance for further investigations in examining the full potential of Tks5 as a relevant prognostic marker in a select number of cancers which may have implications for future targeted therapies.
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Stylli
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Rodney B
authors.initials: RB
authors.lastname: Luwor
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kaye
authors.affiliation: Department of Biochemistry, La Trobe Institute of Molecular Sciences, La Trobe University, Bundoora, Victoria 3086, Australia.
authors.forename: Stacey T T
authors.initials: ST
authors.lastname: I
authors.affiliation: Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hovens
authors.affiliation: Department of Biochemistry, La Trobe Institute of Molecular Sciences, La Trobe University, Bundoora, Victoria 3086, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Lock
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D012189:Retrospective Studies; D015854:Up-Regulation
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C114235:Fish protein, mouse; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins; C478582:SH3PXD2A protein, human