title: Profilin1 regulates invadopodium maturation in human breast cancer cells.
abstract: Invadopodia are actin-driven membrane protrusions that show oscillatory assembly and disassembly causing matrix degradation to support invasion and dissemination of cancer cells in vitro and in vivo. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas and it is been shown that its depletion enhances invasiveness and motility of breast cancer cells by increasing PI(3,4)P2 levels at the leading edge. In this study, we show for the first time that depletion of profilin1 leads to an increase in the number of mature invadopodia and these assemble and disassemble more rapidly than in control cells. Previous work by Sharma et al. (2013a), has shown that the binding of the protein Tks5 with PI(3,4)P2 confers stability to the invadopodium precursor causing it to mature into a degradation-competent structure. We found that loss of profilin1 expression increases the levels of PI(3,4)P2 at the invadopodium and as a result, enhances recruitment of the interacting adaptor Tks5. The increased PI(3,4)P2-Tks5 interaction accelerates the rate of invadopodium anchorage, maturation, and turnover. Our results indicate that profilin1 acts as a molecular regulator of the levels of PI(3,4)P2 and Tks5 recruitment in invadopodia to control the invasion efficiency of invadopodia.
authors.affiliation: Department of Scientific and Technological Research DICTUS, University of Sonora, Hermosillo, Mexico. Electronic address: a.valenzuela.iglesias@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Valenzuela-Iglesias
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States; Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States.
authors.forename: V P
authors.initials: VP
authors.lastname: Sharma
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States.
authors.forename: B T
authors.initials: BT
authors.lastname: Beaty
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Z
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Scientific and Technological Research DICTUS, University of Sonora, Hermosillo, Mexico.
authors.forename: L E
authors.initials: LE
authors.lastname: Gutierrez-Millan
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: P
authors.initials: P
authors.lastname: Roy
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States; Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States. Electronic address: john.condeelis@einstein.yu.edu.
authors.forename: J S
authors.initials: JS
authors.lastname: Condeelis
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States; Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States. Electronic address: jose-javier.bravo@einstein.yu.edu.
authors.forename: J J
authors.initials: JJ
authors.lastname: Bravo-Cordero
mesh_terms: D000199:Actins / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D021961:Cell Membrane Structures / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D051304:Profilins / Q000378:metabolism*
chemical_list: D000199:Actins; D033942:Adaptor Proteins, Vesicular Transport; C495738:PFN1 protein, human; C495741:PFN2 protein, human; D010716:Phosphatidylinositols; D051304:Profilins; C478582:SH3PXD2A protein, human
keywords: Matrix degradation; PI(3,4)P(2); Profilin1; Tks5