CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma

Takamasa Uekita, Masamitsu Tanaka, Misato Takigahira, Yuri Miyazawa, Yukihiro Nakanishi, Yae Kanai, Kazuyoshi Yanagihara, Ryuichi Sakai

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

CUB-domain-containing protein 1 (CDCP1) is a type-I transmembrane protein that is highly expressed in colon, breast, and lung cancers. We recently revealed that CDCP1 is associated with and phosphorylated by Src family kinases and is involved in the regulation of anchorage independence of certain lung cancer cell lines. In this study, we examined whether CDCP1 is involved in the regulation of tumor progression of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Expression and phosphorylation levels of CDCP1 correlated with the invasive potential of scirrhous gastric cancers. Reduction of CDCP1 expression by siRNA suppressed migration, invasion, and anchorage independence without affecting the proliferation of highly invasive scirrhous gastric cancer cells. However, CDCP1 overexpression promoted gastric cancer cell migration with low potential of invasion. Loss of CDCP1 suppressed invasion and dissemination of cancer cells that were orthotopically implanted in the gastric wall of nude mice. Expression and phosphorylation of CDCP1 were also detected in cancer cells of surgically resected tissues of human scirrhous gastric cancer by immunohistochemical analysis. Our results suggest that CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. Therefore, it is both a potential prognostic and therapeutic target in certain types of gastrointestinal cancers, and suppression of its phosphorylation might be a useful strategy for modulating cancer metastasis.

Original languageEnglish
Pages (from-to)1729-1739
Number of pages11
JournalAmerican Journal of Pathology
Volume172
Issue number6
DOIs
Publication statusPublished - 2008 Jun
Externally publishedYes

Fingerprint

Scirrhous Adenocarcinoma
Stomach
Stomach Neoplasms
Phosphorylation
Neoplasms
Cell Movement
Lung Neoplasms
Protein Domains
Gastrointestinal Neoplasms
src-Family Kinases
Nude Mice
Colonic Neoplasms
Small Interfering RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma. / Uekita, Takamasa; Tanaka, Masamitsu; Takigahira, Misato; Miyazawa, Yuri; Nakanishi, Yukihiro; Kanai, Yae; Yanagihara, Kazuyoshi; Sakai, Ryuichi.

In: American Journal of Pathology, Vol. 172, No. 6, 06.2008, p. 1729-1739.

Research output: Contribution to journalArticle

Uekita, T, Tanaka, M, Takigahira, M, Miyazawa, Y, Nakanishi, Y, Kanai, Y, Yanagihara, K & Sakai, R 2008, 'CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma', American Journal of Pathology, vol. 172, no. 6, pp. 1729-1739. https://doi.org/10.2353/ajpath.2008.070981
Uekita, Takamasa ; Tanaka, Masamitsu ; Takigahira, Misato ; Miyazawa, Yuri ; Nakanishi, Yukihiro ; Kanai, Yae ; Yanagihara, Kazuyoshi ; Sakai, Ryuichi. / CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma. In: American Journal of Pathology. 2008 ; Vol. 172, No. 6. pp. 1729-1739.
@article{0bb223e31c534ff08023daba8ee6e327,
title = "CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma",
abstract = "CUB-domain-containing protein 1 (CDCP1) is a type-I transmembrane protein that is highly expressed in colon, breast, and lung cancers. We recently revealed that CDCP1 is associated with and phosphorylated by Src family kinases and is involved in the regulation of anchorage independence of certain lung cancer cell lines. In this study, we examined whether CDCP1 is involved in the regulation of tumor progression of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Expression and phosphorylation levels of CDCP1 correlated with the invasive potential of scirrhous gastric cancers. Reduction of CDCP1 expression by siRNA suppressed migration, invasion, and anchorage independence without affecting the proliferation of highly invasive scirrhous gastric cancer cells. However, CDCP1 overexpression promoted gastric cancer cell migration with low potential of invasion. Loss of CDCP1 suppressed invasion and dissemination of cancer cells that were orthotopically implanted in the gastric wall of nude mice. Expression and phosphorylation of CDCP1 were also detected in cancer cells of surgically resected tissues of human scirrhous gastric cancer by immunohistochemical analysis. Our results suggest that CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. Therefore, it is both a potential prognostic and therapeutic target in certain types of gastrointestinal cancers, and suppression of its phosphorylation might be a useful strategy for modulating cancer metastasis.",
author = "Takamasa Uekita and Masamitsu Tanaka and Misato Takigahira and Yuri Miyazawa and Yukihiro Nakanishi and Yae Kanai and Kazuyoshi Yanagihara and Ryuichi Sakai",
year = "2008",
month = "6",
doi = "10.2353/ajpath.2008.070981",
language = "English",
volume = "172",
pages = "1729--1739",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma

AU - Uekita, Takamasa

AU - Tanaka, Masamitsu

AU - Takigahira, Misato

AU - Miyazawa, Yuri

AU - Nakanishi, Yukihiro

AU - Kanai, Yae

AU - Yanagihara, Kazuyoshi

AU - Sakai, Ryuichi

PY - 2008/6

Y1 - 2008/6

N2 - CUB-domain-containing protein 1 (CDCP1) is a type-I transmembrane protein that is highly expressed in colon, breast, and lung cancers. We recently revealed that CDCP1 is associated with and phosphorylated by Src family kinases and is involved in the regulation of anchorage independence of certain lung cancer cell lines. In this study, we examined whether CDCP1 is involved in the regulation of tumor progression of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Expression and phosphorylation levels of CDCP1 correlated with the invasive potential of scirrhous gastric cancers. Reduction of CDCP1 expression by siRNA suppressed migration, invasion, and anchorage independence without affecting the proliferation of highly invasive scirrhous gastric cancer cells. However, CDCP1 overexpression promoted gastric cancer cell migration with low potential of invasion. Loss of CDCP1 suppressed invasion and dissemination of cancer cells that were orthotopically implanted in the gastric wall of nude mice. Expression and phosphorylation of CDCP1 were also detected in cancer cells of surgically resected tissues of human scirrhous gastric cancer by immunohistochemical analysis. Our results suggest that CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. Therefore, it is both a potential prognostic and therapeutic target in certain types of gastrointestinal cancers, and suppression of its phosphorylation might be a useful strategy for modulating cancer metastasis.

AB - CUB-domain-containing protein 1 (CDCP1) is a type-I transmembrane protein that is highly expressed in colon, breast, and lung cancers. We recently revealed that CDCP1 is associated with and phosphorylated by Src family kinases and is involved in the regulation of anchorage independence of certain lung cancer cell lines. In this study, we examined whether CDCP1 is involved in the regulation of tumor progression of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Expression and phosphorylation levels of CDCP1 correlated with the invasive potential of scirrhous gastric cancers. Reduction of CDCP1 expression by siRNA suppressed migration, invasion, and anchorage independence without affecting the proliferation of highly invasive scirrhous gastric cancer cells. However, CDCP1 overexpression promoted gastric cancer cell migration with low potential of invasion. Loss of CDCP1 suppressed invasion and dissemination of cancer cells that were orthotopically implanted in the gastric wall of nude mice. Expression and phosphorylation of CDCP1 were also detected in cancer cells of surgically resected tissues of human scirrhous gastric cancer by immunohistochemical analysis. Our results suggest that CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. Therefore, it is both a potential prognostic and therapeutic target in certain types of gastrointestinal cancers, and suppression of its phosphorylation might be a useful strategy for modulating cancer metastasis.

UR - http://www.scopus.com/inward/record.url?scp=44849141807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44849141807&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2008.070981

DO - 10.2353/ajpath.2008.070981

M3 - Article

VL - 172

SP - 1729

EP - 1739

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 6

ER -