The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells. Issue 9 (15th May 2018)

• Record Type: Journal Article
• Authors: Okusha, Yuka; Eguchi, Takanori; Sogawa, Chiharu; Okui, Tatsuo; Nakano, Keisuke; Okamoto, Kuniaki; Kozaki, Ken‐Ichi
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 9(2018)
• Page Start: 7363
• Page End: 7376
• Publication Date: 2018-05-15
• Subjects: cancer metastasis -- nuclear MMP -- non‐proteolytic MMP -- PEX domain -- tumor stroma; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27040
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non‐proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor‐stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non‐proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells. Abstract : Profound nuclear localization of MMP3/PEX was found in tumor‐stroma marginal area. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. The non‐proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells.