title: Loss of GM130 in breast cancer cells and its effects on cell migration, invasion and polarity.
abstract: Spatially distinct pools of the small GTPase Cdc42 were observed, but the major focus of research so far has been to investigate its signaling at the plasma membrane. We recently showed that the Golgi pool of Cdc42 is relevant for cell polarity and that it is regulated by GM130, a Golgi matrix protein. Loss of GM130 abrogated cell polarity and consistent with the notion that polarity is frequently impaired in cancer, we found that GM130 is downregulated in colorectal cancer. Whether the loss of GM130 solely affects polarity, or whether it affects other processes relevant for tumorigenesis remains unclear. In a panel of breast cancer cells lines, we investigated the consequences of GM130 depletion on traits of relevance for tumor progression, such as survival, proliferation, adhesion, migration and invasion. We show that cellular assays that depend on polarity, such as chemotaxis and wound scratch assays, are only of limited use to investigate the role of polarity modulators in cancer. Depletion of GM130 increases cellular velocity and increases the invasiveness of breast cancer cells, therefore supporting the view that alterations of polarity contribute to tumor progression.
authors.affiliation: a Biotechnology Institute Thurgau; University of Konstanz ; Kreuzlingen , Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Baschieri
authors.forename: Edith
authors.initials: E
authors.lastname: Uetz-von Allmen
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Legler
authors.forename: Hesso
authors.initials: H
authors.lastname: Farhan
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D049109:Cell Proliferation; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D001324:Autoantigens; C097741:Golgin subfamily A member 2; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004317:Doxorubicin; D020764:cdc42 GTP-Binding Protein