title: Defining the role of TRIP6 in cell physiology and cancer.
abstract: Integrating signals from the ECM (extracellular matrix) via the cell surface into the nucleus is an essential feature of multicellular life and often malfunctions in cancer. To date many signal transducers known as shuttle proteins have been identified that act as both: a cytoskeletal and a signalling protein. Here, we highlight the interesting member of the Zyxin family TRIP6 [thyroid receptor interactor protein 6; also designated ZRP-1 (zyxin-related protein 1)] and review current literature to define its role in cell physiology and cancer. TRIP6 is a versatile scaffolding protein at FAs (focal adhesions) involved in cytoskeletal organization, coordinated cell migration and tissue invasion. Via its LIM and TDC domains TRIP6 interacts with different components of the LPA (lysophosphatidic acid), NF-κB (nuclear factor κB), glucocorticoid and AMPK (AMP-activated protein kinase) signalling pathway and thereby modulates their activity. Within the nucleus TRIP6 acts as a transcriptional cofactor regulating the transcriptional responses of these pathways. Moreover, intranuclear TRIP6 associates with proteins ensuring telomere protection and hence may contribute to genome stability. Accordingly, TRIP6 is engaged in key cellular processes such as cell proliferation, differentiation and survival. These diverse functions of TRIP6 are found to be dysregulated in various cancers and may have pleiotropic roles in tumour initiation, tumour growth and metastasis, which turn TRIP6 into an attractive candidate for cancer diagnosis and targeted therapy.
authors: Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Grombühlstrasse 12, 97080 Würzburg, Germany.
authors: Semjon
authors: S
authors: Willier
authors: Elke
authors: E
authors: Butt
authors: Günther H S
authors: GH
authors: Richter
authors: Stefan
authors: S
authors: Burdach
authors: Thomas G P
authors: TG
authors: Grunewald
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C092282:PSMC5 protein, human; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities