title: Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface.
abstract: The expression of CD9 has been shown to be inversely associated with pancreatic cancer metastasis but the underlying mechanism remains incompletely understood. Using the two closely associated pancreatic cancer cell lines, PaTu-8898s and PaTu-8898t, which are metastatic and non-metastatic, respectively, we showed that the PaTu-8988s cells expressed a lower level of CD9 but had higher proliferation and migration rates than the PaTu-8898t cells. An inverse correlation between CD9 expression and the cell surface level of epidermal growth factor receptor (EGFR) was observed in both cell lines. In the PaTu-8898s cells, overexpression of CD9 decreased the cell surface expression of EGFR, associated with increased expression of dynamin-2, whereas in the PaTu-8898t cells, knockdown of CD9 with RNA interference (RNAi) increased the cell surface expression of EGFR, associated with decreased expression of dynamin-2. However, the total EGFR level did not change by manipulation of CD9 expression, suggesting that CD9 plays a role in EGFR endocytosis. Furthermore, in the PaTu-8898ts cells, CD9 overexpression decreased the cell proliferation and migration, which were reversed by EGFR overexpression, whereas in the PaTu-8898t cells, CD9 knockdown enhanced the cell proliferation and migration which were blocked by EGFR RNAi both in vitro and in vivo. Thus, in pancreatic cancer cells, downregulation of CD9 may play a role in cancer growth and metastasis through, at least in part, enhancing cell surface expression of EGFR.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Maochun
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Guojian
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Congying
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D060245:Tetraspanin 29 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C554869:CD9 protein, human; D060245:Tetraspanin 29; C512478:EGFR protein, human; D066246:ErbB Receptors