title: The role and regulation of Rab40b-Tks5 complex during invadopodia formation and cancer cell invasion.
abstract: Invadopodia formation and extracellular matrix degradation are key events during cancer cell invasion, yet little is known about mechanisms mediating these processes. Here, we report that Rab40b plays a key role in mediating invadopodia function during breast cancer cell invasion. We also identify Tks5 (also known as SH3PXD2A), a known Src kinase substrate, as a new Rab40b effector protein and show that Tks5 functions as a tether that mediates Rab40b-dependent targeting of transport vesicles containing MMP2 and MMP9 to the extending invadopodia. Importantly, we also demonstrate that Rab40b and Tks5 levels are regulated by known tumor suppressor microRNA miR-204. This is the first study that identifies a new Rab40b-Tks5- and miR-204-dependent invadopodia transport pathway that regulates MMP2 and MMP9 secretion, and extracellular matrix remodeling during cancer progression.
authors: Department of Cell and Developmental Biology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA.
authors: Abitha
authors: A
authors: Jacob
authors: Department of Cell and Developmental Biology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA.
authors: Erik
authors: E
authors: Linklater
authors: Department of Cell and Developmental Biology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA.
authors: Brian A
authors: BA
authors: Bayless
authors: Department of Medicine/Division of Medical Oncology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA.
authors: Traci
authors: T
authors: Lyons
authors: Department of Cell and Developmental Biology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA Rytis.Prekeris@ucdenver.edu.
authors: Rytis
authors: 0000-0003-3393-1963
authors: R
authors: Prekeris
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000069261:Podosomes / Q000378:metabolism*; D000072417:Protein Domains; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; C478582:SH3PXD2A protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020691:rab GTP-Binding Proteins
keywords: Invadopodia; MMP2; MMP9; Metastasis; Rab40b; Tks5