Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis

Yun Gao, Kyoko Kitagawa, Yoshihiro Hiramatsu, Hirotoshi Kikuchi, Tomoyasu Isobe, Mai Shimada, Chiharu Uchida, Takayuki Hattori, Toshiaki Oda, Keiko Nakayama, Keiichi I. Nakayama, Tatsuo Tanaka, Hiroyuki Konno, Masatoshi Kitagawa

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

A reduced expression level of the cyclin-dependent kinase inhibitor p27Kip1 is associated with increased tumor malignancy and poor prognosis in individuals with various types of cancer. To investigate the basis for this relation, we applied microarray analysis to screen for genes differentially expressed between p27+/- and parental (p27 +/+) HCT116 human colon carcinoma cells. Expression of the gene for G protein-coupled receptor 48 (GPR48) was increased in the p27+/- cells. Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas. GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target.

Original languageEnglish
Pages (from-to)11623-11631
Number of pages9
JournalCancer Research
Volume66
Issue number24
DOIs
Publication statusPublished - Dec 15 2006

Fingerprint

G-Protein-Coupled Receptors
Up-Regulation
Down-Regulation
Neoplasm Metastasis
Carcinoma
Colon
HCT116 Cells
Lewis Lung Carcinoma
Neoplasms
Cyclin-Dependent Kinases
Microarray Analysis
RNA Interference
Lymph Nodes
Lung
Genes
Proteins
In Vitro Techniques
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Gao, Y., Kitagawa, K., Hiramatsu, Y., Kikuchi, H., Isobe, T., Shimada, M., ... Kitagawa, M. (2006). Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis. Cancer Research, 66(24), 11623-11631. https://doi.org/10.1158/0008-5472.CAN-06-2629

Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis. / Gao, Yun; Kitagawa, Kyoko; Hiramatsu, Yoshihiro; Kikuchi, Hirotoshi; Isobe, Tomoyasu; Shimada, Mai; Uchida, Chiharu; Hattori, Takayuki; Oda, Toshiaki; Nakayama, Keiko; Nakayama, Keiichi I.; Tanaka, Tatsuo; Konno, Hiroyuki; Kitagawa, Masatoshi.

In: Cancer Research, Vol. 66, No. 24, 15.12.2006, p. 11623-11631.

Research output: Contribution to journalArticle

Gao, Y, Kitagawa, K, Hiramatsu, Y, Kikuchi, H, Isobe, T, Shimada, M, Uchida, C, Hattori, T, Oda, T, Nakayama, K, Nakayama, KI, Tanaka, T, Konno, H & Kitagawa, M 2006, 'Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis', Cancer Research, vol. 66, no. 24, pp. 11623-11631. https://doi.org/10.1158/0008-5472.CAN-06-2629
Gao, Yun ; Kitagawa, Kyoko ; Hiramatsu, Yoshihiro ; Kikuchi, Hirotoshi ; Isobe, Tomoyasu ; Shimada, Mai ; Uchida, Chiharu ; Hattori, Takayuki ; Oda, Toshiaki ; Nakayama, Keiko ; Nakayama, Keiichi I. ; Tanaka, Tatsuo ; Konno, Hiroyuki ; Kitagawa, Masatoshi. / Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis. In: Cancer Research. 2006 ; Vol. 66, No. 24. pp. 11623-11631.
@article{4947e43f58a74d9bb0e10da196f689d3,
title = "Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis",
abstract = "A reduced expression level of the cyclin-dependent kinase inhibitor p27Kip1 is associated with increased tumor malignancy and poor prognosis in individuals with various types of cancer. To investigate the basis for this relation, we applied microarray analysis to screen for genes differentially expressed between p27+/- and parental (p27 +/+) HCT116 human colon carcinoma cells. Expression of the gene for G protein-coupled receptor 48 (GPR48) was increased in the p27+/- cells. Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas. GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target.",
author = "Yun Gao and Kyoko Kitagawa and Yoshihiro Hiramatsu and Hirotoshi Kikuchi and Tomoyasu Isobe and Mai Shimada and Chiharu Uchida and Takayuki Hattori and Toshiaki Oda and Keiko Nakayama and Nakayama, {Keiichi I.} and Tatsuo Tanaka and Hiroyuki Konno and Masatoshi Kitagawa",
year = "2006",
month = "12",
day = "15",
doi = "10.1158/0008-5472.CAN-06-2629",
language = "English",
volume = "66",
pages = "11623--11631",
journal = "Cancer Research",
issn = "0008-5472",
number = "24",

}

TY - JOUR

T1 - Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis

AU - Gao, Yun

AU - Kitagawa, Kyoko

AU - Hiramatsu, Yoshihiro

AU - Kikuchi, Hirotoshi

AU - Isobe, Tomoyasu

AU - Shimada, Mai

AU - Uchida, Chiharu

AU - Hattori, Takayuki

AU - Oda, Toshiaki

AU - Nakayama, Keiko

AU - Nakayama, Keiichi I.

AU - Tanaka, Tatsuo

AU - Konno, Hiroyuki

AU - Kitagawa, Masatoshi

PY - 2006/12/15

Y1 - 2006/12/15

N2 - A reduced expression level of the cyclin-dependent kinase inhibitor p27Kip1 is associated with increased tumor malignancy and poor prognosis in individuals with various types of cancer. To investigate the basis for this relation, we applied microarray analysis to screen for genes differentially expressed between p27+/- and parental (p27 +/+) HCT116 human colon carcinoma cells. Expression of the gene for G protein-coupled receptor 48 (GPR48) was increased in the p27+/- cells. Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas. GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target.

AB - A reduced expression level of the cyclin-dependent kinase inhibitor p27Kip1 is associated with increased tumor malignancy and poor prognosis in individuals with various types of cancer. To investigate the basis for this relation, we applied microarray analysis to screen for genes differentially expressed between p27+/- and parental (p27 +/+) HCT116 human colon carcinoma cells. Expression of the gene for G protein-coupled receptor 48 (GPR48) was increased in the p27+/- cells. Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas. GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target.

UR - http://www.scopus.com/inward/record.url?scp=33846209564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846209564&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-06-2629

DO - 10.1158/0008-5472.CAN-06-2629

M3 - Article

C2 - 17178856

AN - SCOPUS:33846209564

VL - 66

SP - 11623

EP - 11631

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 24

ER -