The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells

• Published in: Journal of cellular biochemistry Vol. 119; no. 9; pp. 7363 - 7376
• Main Authors: Okusha, Yuka, Eguchi, Takanori, Sogawa, Chiharu, Okui, Tatsuo, Nakano, Keisuke, Okamoto, Kuniaki, Kozaki, Ken‐Ichi
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2018
• Subjects: Adenocarcinoma; Cancer; cancer metastasis; Cell adhesion & migration; Cell migration; Cell proliferation; Colon; Gelatinase B; Gene expression; Intracellular signalling; Isoforms; Localization; Lungs; Matrix metalloproteinase; Metalloproteinase; Metastases; Metastasis; non‐proteolytic MMP; nuclear MMP; Nuclei (cytology); PEX domain; Proteolysis; Stroma; Stromelysin 1; Transcription; Tumor cell lines; tumor stroma; Tumors; non-proteolytic MMP; nuclear MMP; tumor stroma; PEX domain; cancer metastasis
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27040

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. 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.