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A potential role for synaptotagmin XIII (SYT13) in epithelial‐mesenchymal transition
Author(s) -
Jahn Jennifer E.,
Coleman William B.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a202
Subject(s) - biology , microbiology and biotechnology , epithelial–mesenchymal transition , contact inhibition , mesenchymal stem cell , cadherin , phenotype , transfection , transcription factor , cancer research , progenitor cell , cell culture , cell , downregulation and upregulation , gene , genetics , stem cell
Multipotent WB‐F344 rat liver epithelial progenitor cells are anchorage‐dependent, contact‐inhibited, and grow in a smooth monolayer. Neoplastic transformation of these cells and passage through neonatal rats resulted in outgrowth of tumor cells, including GN6TF which exhibit a fibroblastic morphology, loss of contact inhibition, and anchorage‐independent growth. Molecular alterations associated with the WB‐F344 to GN6TF progression include loss of WT1 expression. WT1 is a transcription factor and regulator of epithelial‐mesenchymal transition (EMT) in kidney. Introduction of human 11p11.2 into GN6TF cells produced microcell hybrid clones (MCH) with a normalized phenotype, and both E‐cadherin and WT1 were induced. Deletion/transcription mapping of MCHs identified SYT13 as the potential effector of the EMT. RNAi was employed to stably silence SYT13 in MCH cell lines, resulting in loss of contact‐inhibition, anchorage‐independent growth, and reexpression of tumorigenicity, accompanied by loss of E‐cadherin and WT1 expression. Transfection of GN6TF cells with BACs containing SYT13 resulted in normalization of cell phenotype accompanied by induction of E‐cadherin and WT1. These results combine to suggest that neoplastic transformation of WB‐F344 cells leading to outgrowth of GN6TF cells involves an EMT, and that SYT13 may be involved through direct or indirect induction of WT1. Support: NIH CA78343.