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

Yuka Okusya; Takanori Eguchi; Chiharu Sogawa; Tatsuo Okui; Keisuke Nakano; Kuniaki Okamoto; Ken-ichi Kozaｋi

doi:10.1002/jcb.27040

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

Yuka Okusya, Takanori Eguchi, Chiharu Sogawa, Tatsuo Okui, Keisuke Nakano, Kuniaki Okamoto, Ken-ichi Kozaｋi

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

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.

Original language	English
Pages (from-to)	7363-7376
Number of pages	14
Journal	Journal of Cellular Biochemistry
Volume	119
Issue number	9
DOIs	https://doi.org/10.1002/jcb.27040
Publication status	Published - Sept 2018

Keywords

PEX domain
cancer metastasis
non-proteolytic MMP
nuclear MMP
tumor stroma

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/jcb.27040

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@article{cc2e0bfee7b44fd490f8dec50c937d71,

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

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.",

keywords = "PEX domain, cancer metastasis, non-proteolytic MMP, nuclear MMP, tumor stroma",

author = "Yuka Okusya and Takanori Eguchi and Chiharu Sogawa and Tatsuo Okui and Keisuke Nakano and Kuniaki Okamoto and Ken-ichi Kozaｋi",

note = "Funding Information: This paper is dedicated to the memory of one of the coauthors, Professor Ken-ichi Kozaki, who passed away on May 29, 2016. The authors thank Kisho Ono, Toshifumi Fujiwara, Yuri Namba, Tomoko Yamamoto and Kazumi Ohyama for their technical assistance and useful discussion. This work was supported by JSPS KAKENHI, grant numbers JP17K17895 (to YO), JP17K11642 (to TE), JP26293067 (to KK), JP26670815 (to KK), Start-up Grant for Young Scientists at Okayama Univ. (to YO), Molecular Imaging Micro Dose Phase 0 Grant at Okayama Univ. (to YO and KK), Gender Equality Grant at Okayama Univ. (to YO), and a Ryobi Teien Memorial Foundation Grant (to TE). Funding Information: Ryobi Teien Memorial Foundation; A Ryobi Teien Memorial Foundation Grant; Japan Society for the Promotion of Science, Grant numbers: JP17K11642, JP17K17895, JP26293067, JP26670815; Okayama Univ. Gender Equality Grant, Molecular Imaging Micro Dose Phase 0 Grant, Start-up Grant for Young Scientists Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",

year = "2018",

month = sep,

doi = "10.1002/jcb.27040",

language = "English",

volume = "119",

pages = "7363--7376",

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T1 - The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells

AU - Okusya, Yuka

AU - Eguchi, Takanori

AU - Sogawa, Chiharu

AU - Okui, Tatsuo

AU - Nakano, Keisuke

AU - Okamoto, Kuniaki

AU - Kozaｋi, Ken-ichi

N1 - Funding Information: This paper is dedicated to the memory of one of the coauthors, Professor Ken-ichi Kozaki, who passed away on May 29, 2016. The authors thank Kisho Ono, Toshifumi Fujiwara, Yuri Namba, Tomoko Yamamoto and Kazumi Ohyama for their technical assistance and useful discussion. This work was supported by JSPS KAKENHI, grant numbers JP17K17895 (to YO), JP17K11642 (to TE), JP26293067 (to KK), JP26670815 (to KK), Start-up Grant for Young Scientists at Okayama Univ. (to YO), Molecular Imaging Micro Dose Phase 0 Grant at Okayama Univ. (to YO and KK), Gender Equality Grant at Okayama Univ. (to YO), and a Ryobi Teien Memorial Foundation Grant (to TE). Funding Information: Ryobi Teien Memorial Foundation; A Ryobi Teien Memorial Foundation Grant; Japan Society for the Promotion of Science, Grant numbers: JP17K11642, JP17K17895, JP26293067, JP26670815; Okayama Univ. Gender Equality Grant, Molecular Imaging Micro Dose Phase 0 Grant, Start-up Grant for Young Scientists Publisher Copyright: © 2018 Wiley Periodicals, Inc.

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

KW - PEX domain

KW - cancer metastasis

KW - non-proteolytic MMP

KW - nuclear MMP

KW - tumor stroma

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U2 - 10.1002/jcb.27040

DO - 10.1002/jcb.27040

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C2 - 29761931

AN - SCOPUS:85053524033

SN - 0730-2312

VL - 119

SP - 7363

EP - 7376

JO - Journal of supramolecular structure and cellular biochemistry

JF - Journal of supramolecular structure and cellular biochemistry

IS - 9

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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