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Research Papers:

Filamin C promotes lymphatic invasion and lymphatic metastasis and increases cell motility by regulating Rho GTPase in esophageal squamous cell carcinoma

Kan Tanabe, Yoshinari Shinsato, Tatsuhiko Furukawa _, Yoshiaki Kita, Kazuhito Hatanaka, Kentaro Minami, Kohichi Kawahara, Masatatsu Yamamoto, Kenji Baba, Shinichiro Mori, Yasuto Uchikado, Kosei Maemura, Akihide Tanimoto and Shoji Natsugoe

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Oncotarget. 2017; 8:6353-6363. https://doi.org/10.18632/oncotarget.14087

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Abstract

Kan Tanabe1,2,*, Yoshinari Shinsato2,*, Tatsuhiko Furukawa2,4, Yoshiaki Kita1, Kazuhito Hatanaka3, Kentaro Minami2, Kohichi Kawahara2, Masatatsu Yamamoto2, Kenji Baba1, Shinichiro Mori1, Yasuto Uchikado1, Kosei Maemura1, Akihide Tanimoto3, Shoji Natsugoe1

1Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

2Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

3Department of Molecular and Cellular Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

4Center for the Research of Advanced Diagnosis and Therapy of Cancer, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

*These authors contributed equally to this work

Correspondence to:

Tatsuhiko Furukawa, email: furukawa@m3.kufm.kagoshima-u.ac.jp

Keywords: FLNC, ESCC, Rac1, Cdc42, migration

Received: September 08, 2016     Accepted: December 13, 2016     Published: December 22, 2016

ABSTRACT

To establish treatments to improve the prognosis of cancer patients, it is necessary to find new targets to control metastasis. We found that expression of FilaminC (FLNC), a member of the actin binding and cross-linking filamin protein family is correlated with lymphatic invasion and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC) by increasing cell motility through activation of Rho GTPase.

Immunohistochemistry analysis showed that FLNC expression in ESCC is associated with lymphatic invasion, metastasis, and prognosis. FLNC knockdown in esophageal cancer cell lines decreased cell migration in wound healing and transwell migration assays, and invasion in transwell migration assays. Furthermore, FLNC knockdown reduced the amount of activated Rac-1 (GTP-Rac1) and activated Cdc42 (GTP-Cdc42). Our results suggest that FLNC expression is a useful biomarker of ESCC metastatic tendency and that inhibiting FLNC function may be useful to control the metastasis of ESCC.


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