SCG10-like protein (SCLIP) is a STAT3-interacting protein involved in maintaining epithelial morphology in MCF-7 breast cancer cells.
STAT (signal transducer and activator of transcription) 3 is a key contributor to cancer cell migration and invasion, with excessive STAT3 activity promoting growth arrest, cell-cell dissociation and increased migration of breast cancer epithelial cells. The STAT3-regulated mechanisms involved in this process, however, are not fully defined. Previously, we had revealed SCLIP [SCG10 (superior cervical ganglia protein 10)-like protein] as a novel STAT3-interacting protein. In the present study, we show that STAT3 binds the C-terminal tubulin-associating region of SCLIP. In a search for a function of SCLIP, we show that SCLIP was down-regulated during OSM (oncostatin M) treatment in MCF-7 cells, which also stimulates epithelial morphology loss. SCLIP knockdown likewise triggered a loss of epithelial morphology which included reduced E-cadherin expression. We found that STAT3 was required to maintain SCLIP stability. Furthermore, inhibition of OSM-induced STAT3 activity preserved SCLIP expression and MCF-7 epithelial monolayers. Taken together, we propose that a STAT3-SCLIP interaction is required to preserve SCLIP stability and contributes to the maintenance of normal epithelial morphology. Disruption of the STAT3-SCLIP interaction with OSM may contribute to cytokine-mediated loss in cell-cell attachment and morphology transition in MCF-7 cells.
Ng
Dominic C H
DC
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, VIC, Australia 3010. ngd@unimelb.edu.au
Lim
Cheh P
CP
Lin
Bao H
BH
Zhang
Tong
T
Cao
Xinmin
X
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D053683:Oncostatin M / Q000494:pharmacology; D016716:PC12 Cells; D011485:Protein Binding / Q000187:drug effects; D034622:RNA Interference; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C112285:STMN3 protein, human; D050777:Stathmin; D053683:Oncostatin M; D008156:Luciferases