title: EPLIN is a crucial regulator for extrusion of RasV12-transformed cells.
abstract: At the initial stage of carcinogenesis, a mutation occurs in a single cell within a normal epithelial layer. We have previously shown that RasV12-transformed cells are apically extruded from the epithelium when surrounded by normal cells. However, the molecular mechanisms underlying this phenomenon remain elusive. Here, we demonstrate that Cav-1-containing microdomains and EPLIN (also known as LIMA1) are accumulated in RasV12-transformed cells that are surrounded by normal cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion of RasV12-transformed cells, suggesting their positive role in the elimination of transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects its enrichment in RasV12-transformed cells that are surrounded by normal cells. Furthermore, EPLIN regulates non-cell-autonomous activation of myosin-II and protein kinase A (PKA) in RasV12-transformed cells. In addition, EPLIN substantially affects the accumulation of filamin A, a vital player in epithelial defense against cancer (EDAC), in the neighboring normal cells, and vice versa. These results indicate that EPLIN is a crucial regulator of the interaction between normal and transformed epithelial cells.
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ohoka
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kajita
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Ikenouchi
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yako
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Kitamoto
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kon
authors.affiliation: Genomics, Proteomics and Biomedical Functions, Department of Life and Medical Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Tataramiyakodani, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Ikegawa
authors.affiliation: Shimadzu Corporation, Life Science Research Center, 1-3 Kanda, Nishiki-cho, Chiyoda-ku, Tokyo 101-8448, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan yasu@igm.hokudai.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002867:Chromones / Q000494:pharmacology; D058967:Contactin 1 / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D064448:Filamins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D061985:Madin Darby Canine Kidney Cells; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D024462:Myosin Type II / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D002070:Butadienes; D051242:Caveolin 1; D002867:Chromones; D058967:Contactin 1; D004791:Enzyme Inhibitors; D064448:Filamins; D008840:Microfilament Proteins; D009025:Morpholines; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D024462:Myosin Type II; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Apical extrusion; Cav-1; EPLIN; Epithelial cell; Ras