The N-cadherin cytoplasmic domain confers anchorage-independent growth and the loss of contact inhibition.
Tumor growth is characterized by anchorage independence and the loss of contact inhibition. Previously, we showed that either a red fluorescent protein (DsRed)-tagged N-cadherin or E-cadherin cytoplasmic domain (DNCT or DECT) could function as a dominant negative inhibitor by blocking the cell surface localization of endogenous E-cadherin and inducing cell dissociation. Here, we show that expression of DNCT abrogated contact inhibition of proliferation and conferred anchorage-independent growth. DNCT expression induced the relocation of the tumor suppressor Merlin from the cell surface to intracellular compartments. Although DNCT expression induced redistribution of TAZ from the cytoplasm to the nucleus, YAP/TAZ signaling was not activated. An E-cadherin-α-catenin chimera that functions as a β-catenin-independent cell adhesion molecule restored contact inhibition and anchorage-dependency of growth. Addition of the SV40 large T antigen nuclear localization signal reversed the effects of DNCT expression, indicating that DNCT functioned outside of the nucleus.
Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Masayuki
M
Ozawa
D000818:Animals; D023102:Anoikis / Q000235:genetics; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D003260:Contact Inhibition / Q000235:genetics; D015870:Gene Expression; D017930:Genes, Reporter; D042541:Intracellular Space / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D025581:Neurofibromin 2 / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D021381:Protein Transport; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D015533:Transcriptional Activation; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin
D015820:Cadherins; D015815:Cell Adhesion Molecules; D025581:Neurofibromin 2; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin; D051176:beta Catenin; D020928:Mitogen-Activated Protein Kinases