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KIFC1 regulates ZWINT to promote tumor progression and spheroid formation in colorectal cancer.
Akabane, Shintaro; Oue, Naohide; Sekino, Yohei; Asai, Ryuichi; Thang, Pham Quoc; Taniyama, Daiki; Sentani, Kazuhiro; Yukawa, Masashi; Toda, Takashi; Kimura, Ken-Ichi; Egi, Hiroyuki; Shimizu, Wataru; Ohdan, Hideki; Yasui, Wataru.
Afiliação
  • Akabane S; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Oue N; Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Sekino Y; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Asai R; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Thang PQ; Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan.
  • Taniyama D; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Sentani K; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Yukawa M; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Toda T; Hiroshima Research Center for Healthy Aging, Department of Molecular Biotechnology, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan.
  • Kimura KI; Hiroshima Research Center for Healthy Aging, Department of Molecular Biotechnology, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan.
  • Egi H; Chemical Biology Laboratory, Graduate School of Arts and Sciences, Iwate University, Iwate, Japan.
  • Shimizu W; Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Ohdan H; Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Yasui W; Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Pathol Int ; 71(7): 441-452, 2021 Jul.
Article em En | MEDLINE | ID: mdl-33819373
ABSTRACT
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Kinesin Family Member C1 (KIFC1) has been proposed as a promising therapeutic target due to its pivotal role in centrosome clustering to mediate cancer cell progression. This study aimed to analyze the expression and biological function of KIFC1 in CRC. Immunohistochemically, 67 (52%) of 129 CRC cases were positive for KIFC1 and statistically associated with poorer overall survival. KIFC1 small interfering RNA (siRNA)-transfected cells demonstrated lower cell proliferation as compared to the negative control cells. A specific KIFC1 inhibitor, kolavenic acid analog (KAA) drastically inhibited CRC cell proliferation. Microarray analysis revealed that KAA-treated CRC cells presented reduced ZW10 interacting kinetochore protein (ZWINT) expression as compared to control cells. Immunohistochemical analysis demonstrated that 61 (47%) of 129 CRC cases were positive for ZWINT and ZWINT expression was significantly correlated with KIFC1 expression. ZWINT-positive cases exhibited significantly worse overall survival. KIFC1 siRNA-transfected cells showed reduced ZWINT expression while ZWINT siRNA-transfected cells decreased cell proliferation. Both KIFC1 and ZWINT knockdown cells attenuated spheroid formation ability. This study provides new insights into KIFC1 regulating ZWINT in CRC progression and its potential as a therapeutic target.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Neoplasias Colorretais / Cinesinas / Peptídeos e Proteínas de Sinalização Intracelular Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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XML
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Neoplasias Colorretais / Cinesinas / Peptídeos e Proteínas de Sinalização Intracelular Idioma: En Ano de publicação: 2021 Tipo de documento: Article