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Regulation of Carcinoma Invasion by ADAMs and MMPs
Author(s) -
Toker Alex
Publication year - 2009
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.23.1_supplement.94.2
Subject(s) - matrix metalloproteinase , cancer research , proteases , stromal cell , biology , metastasis , cell migration , breast carcinoma , tumor progression , downregulation and upregulation , cancer cell , cancer , breast cancer , microbiology and biotechnology , cell culture , genetics , biochemistry , gene , enzyme
The metastatic dissemination of carcinoma cells is regulated by numerous genetic and epigenetic events. The acquisition of a mesenchymal phenotype is concomitant with a propensity of cells to undergo invasive migration. Studies have revealed that matrix proteases operate at the tumor‐stromal boundary. Two families of matrix proteases that are crucial for invasive migration are the ADAMs (A Disintegrin and Metalloproteinase) and MMPs (Matrix Metalloproteinases), which are secreted by either tumor cells or by the stroma. ADAM9 is upregulated in a large number of breast tumors and cell lines. We have shown that ADAM9 is highly expressed in tumor cell lines, and expression and shRNA studies show that ADAM9 promotes invasive migration of breast cancer cells. An analysis of the functional mechanisms by which ADAM9 promotes invasive migration will be presented. We have also found that the transcriptional factor FOXO3a induces the expression of MMP‐13. In turn, this promotes the invasive migration of breast cancer cells. In vivo studies and pathological examination of tumors show that FOXO3a and MMP‐13 are highly expressed in breast tumors. Thus, ADAMs and MMPs are crucial for the efficient dissemination of highly aggressive carcinoma cells.