title: N-cadherin regulates mammary tumor cell migration through Akt3 suppression.
abstract: N-cadherin is a cell-cell adhesion molecule that plays a role in breast cancer metastasis. Here, we show that in vivo expression of N-cadherin in the PyMT mouse model, which enhances mammary tumor metastasis, results in selective inhibition of Akt3 expression and phosphorylation. Similarly, exogenous expression of N-cadherin in PyMT or MCF-7 mammary tumor cells enhanced cell motility and caused a dramatic reduction in Akt3 expression and phosphorylation. Moreover, knockdown of Akt3 in PyMT tumor cells increased cell motility and disrupted mammary morphogenesis, but had no effect on cell proliferation. Conversely, overexpression of wild-type Akt3 in PyMT-N-cadherin cells inhibited cell motility promoted by N-cadherin. Taken altogether, these findings demonstrate that N-cadherin suppresses Akt3 to promote cell motility and highlight the intricate regulation of Akt isoforms by N-cadherin during metastasis.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chung
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.forename: K
authors.initials: K
authors.lastname: Suyama
authors.forename: S
authors.initials: S
authors.lastname: Bajaj
authors.forename: X
authors.initials: X
authors.lastname: Qian
authors.forename: O D
authors.initials: OD
authors.lastname: Loudig
authors.forename: E A
authors.initials: EA
authors.lastname: Eugenin
authors.forename: G R
authors.initials: GR
authors.lastname: Phillips
authors.forename: R B
authors.initials: RB
authors.lastname: Hazan
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D017468:Receptors, Fibroblast Growth Factor; C491753:Akt3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt