title: S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells.
abstract: Cell migration and invasion require increased plasma membrane dynamics and ability to navigate through dense stroma, thereby exposing plasma membrane to tremendous physical stress. Yet, it is largely unknown how metastatic cancer cells acquire an ability to cope with such stress. Here we show that S100A11, a calcium-binding protein upregulated in a variety of metastatic cancers, is essential for efficient plasma membrane repair and survival of highly motile cancer cells. Plasma membrane injury-induced entry of calcium into the cell triggers recruitment of S100A11 and Annexin A2 to the site of injury. We show that S100A11 in a complex with Annexin A2 helps reseal the plasma membrane by facilitating polymerization of cortical F-actin and excision of the damaged part of the plasma membrane. These data reveal plasma membrane repair in general and S100A11 and Annexin A2 in particular as new targets for the therapy of metastatic cancers.
authors.affiliation: Children's National Medical Center, Center for Genetic Medicine Research, 111 Michigan Avenue, NW, Washington, District of Columbia 20010-2970, USA.
authors.forename: Jyoti K
authors.initials: JK
authors.lastname: Jaiswal
authors.affiliation: Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
authors.forename: Stine P
authors.initials: SP
authors.lastname: Lauritzen
authors.affiliation: Children's National Medical Center, Center for Genetic Medicine Research, 111 Michigan Avenue, NW, Washington, District of Columbia 20010-2970, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Scheffer
authors.affiliation: Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kitaku, 2-5-1 Shikajta-cho, Okayama 700-8558, Japan.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Bunkenborg
authors.affiliation: Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Simon
authors.affiliation: Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
authors.forename: Tuula
authors.initials: T
authors.lastname: Kallunki
authors.affiliation: Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
authors.forename: Marja
authors.initials: M
authors.lastname: Jäättelä
authors.affiliation: Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Nylandsted
mesh_terms: D000199:Actins / Q000378:metabolism; D017306:Annexin A2 / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000473:pathology*; D002465:Cell Movement; D006367:HeLa Cells; D006801:Humans; D017136:Ion Transport; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D009418:S100 Proteins / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D000199:Actins; D017306:Annexin A2; D002118:Calcium; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D009418:S100 Proteins; C472822:ANXA2 protein, human; C072337:S100A11 protein, human; C508053:ERBB2 protein, human