Oncotarget

Research Papers:

Hematopoietic lineage cell-specific protein 1 (HS1), a hidden player in migration, invasion, and tumor formation, is over-expressed in ovarian carcinoma cells

Yoshihiro Koya _, Wenting Liu, Yoshihiko Yamakita, Takeshi Senga, Kiyosumi Shibata, Mamoru Yamashita, Akihiro Nawa, Fumitaka Kikkawa and Hiroaki Kajiyama

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Oncotarget. 2018; 9:32609-32623. https://doi.org/10.18632/oncotarget.25975

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Abstract

Yoshihiro Koya1,2, Wenting Liu1,2, Yoshihiko Yamakita1,2, Takeshi Senga3, Kiyosumi Shibata4, Mamoru Yamashita2, Akihiro Nawa1,2, Fumitaka Kikkawa5 and Hiroaki Kajiyama5

1Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

2Bell Research Center for Reproductive Health and Cancer, Nagoya, Aichi, Japan

3Yahagigawa Hospital, Anjo, Aichi, Japan

4Department of Obstetrics and Gynecology, Fujita Health University, Banbuntane Hotokukai Hospital, Nakagawa-ku, Nagoya, Japan

5Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

Correspondence to:

Yoshihiro Koya, email: koya.yoshihiro@c.mbox.nagoya-u.ac.jp

Hiroaki Kajiyama, email: kajiyama@med.nagoya-u.ac.jp

Keywords: epithelial ovarian cancer (EOC); migration/invasion; cytoskeletal protein; tumor formation; prognostic factor

Received: March 29, 2018     Accepted: July 31, 2018     Published: August 24, 2018

ABSTRACT

Hematopoietic lineage cell-specific protein 1 (HS1), which is the hematopoietic homolog of cortactin, is an actin-binding protein and Lyn substrate. It is upregulated in several cancers and its expression level is associated with increased cell migration, metastasis, and poor prognosis. Here we investigated the expression and roles of HS1 in ovarian carcinoma cells. We analyzed the expression of HS1 in 171 ovarian cancer specimens and determined the association between HS1 expression and clinicopathological characteristics, including patient outcomes. In patients with stage II–IV disease, positive HS1 expression was associated with significantly worse overall survival than negative expression (P < 0.05). HS1 was localized in invadopodia in some ovarian cancer cells and was required for invadopodia formation. Migration and invasion of ovarian cancer cells were suppressed by down-regulation of HS1, but increased in cells that over-expressed exogenous HS1. Furthermore, ovarian cancer cells that expressed HS1 shRNA exhibited reduced tumor formation in a mouse xenograft model. Finally, we found that tyrosine phosphorylation of HS1 was essential for cell migration and invasion. These findings show that HS1 is a useful biomarker for the prognosis of patients with ovarian carcinoma and is a critical regulator of cytoskeleton remodeling involved in cell migration and invasion.


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