title: CAP1 (Cyclase-Associated Protein 1) Exerts Distinct Functions in the Proliferation and Metastatic Potential of Breast Cancer Cells Mediated by ERK.
abstract: The actin-regulating protein CAP1 is implicated in the invasiveness of human cancers. However, the exact role remains elusive and controversial given lines of conflicting evidence. Moreover, a potential role in the proliferative transformation has largely been overlooked. Further establishing the role and dissecting underlying mechanisms are imperative before targeting CAP1 can become a possibility for cancer treatment. Here we report our findings that CAP1 exerts cell type-dependent functions in the invasiveness of breast cancer cells. Depletion of CAP1 in the metastatic MDA-MB-231 and BT-549 cancer cells stimulated the metastatic potential while it actually inhibited it in the non-metastatic MCF-7 cancer cells or in normal cells. Moreover, we demonstrate functions for CAP1 in cancer cell proliferation and anchorage-independent growth, again in a cell context-dependent manner. Importantly, we identify pivotal roles for the ERK-centered signaling in mediating both CAP1 functions. Phosphor mutants of CAP1 at the S307/S309 regulatory site had compromised rescue effects for both the invasiveness and proliferation in CAP1-knockdown cells, suggesting that CAP1 likely mediates upstream cell signals to control both functions. These novel mechanistic insights may ultimately open up avenues for strategies targeting CAP1 in the treatment of breast cancer, tailored for specific types of the highly diverse disease.
authors.affiliation: Department of Biological Sciences, Arkansas State University, State University, AR 72467, USA.|Molecular Biosciences Program, Arkansas State University, State University, AR 72467, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, Arkansas State University, State University, AR 72467, USA.|Molecular Biosciences Program, Arkansas State University, State University, AR 72467, USA.
authors.forename: Guo-Lei
authors.initials: GL
authors.lastname: Zhou
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D010766:Phosphorylation
chemical_list: C489549:CAP1 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins