Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma

Yu Chih Chao, Szu Hua Pan, Shuenn Chen Yang, Sung Liang Yu, Ting Fang Che, Chung Wu Lin, Mu Shiun Tsai, Gee Chen Chang, Che Hsiang Wu, Yi Ying Wu, Yung Chie Lee, Tse-Ming Hong, Pan Chyr Yang

Research output: Contribution to journalArticle

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Abstract

Rationale: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. Objectives: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. Methods: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. Measurements and Main Results: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-α], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. Conclusions: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.

Original languageEnglish
Pages (from-to)123-133
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume179
Issue number2
DOIs
Publication statusPublished - 2009 Jan 15

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Claudin-1
Neoplasm Metastasis
Neoplasms
Cell Movement
Immunohistochemistry
Time-Lapse Imaging
Occludin
Thrombospondin 1
Connective Tissue Growth Factor
Messenger RNA
Transforming Growth Factor alpha
Osteopontin
Aptitude
Survival
Facilitative Glucose Transport Proteins
Adenocarcinoma of lung
Tight Junctions
Homeobox Genes
Herpes Zoster
Liver Neoplasms

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Chao, Yu Chih ; Pan, Szu Hua ; Yang, Shuenn Chen ; Yu, Sung Liang ; Che, Ting Fang ; Lin, Chung Wu ; Tsai, Mu Shiun ; Chang, Gee Chen ; Wu, Che Hsiang ; Wu, Yi Ying ; Lee, Yung Chie ; Hong, Tse-Ming ; Yang, Pan Chyr. / Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma. In: American Journal of Respiratory and Critical Care Medicine. 2009 ; Vol. 179, No. 2. pp. 123-133.
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title = "Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma",
abstract = "Rationale: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. Objectives: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. Methods: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. Measurements and Main Results: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-α], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. Conclusions: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.",
author = "Chao, {Yu Chih} and Pan, {Szu Hua} and Yang, {Shuenn Chen} and Yu, {Sung Liang} and Che, {Ting Fang} and Lin, {Chung Wu} and Tsai, {Mu Shiun} and Chang, {Gee Chen} and Wu, {Che Hsiang} and Wu, {Yi Ying} and Lee, {Yung Chie} and Tse-Ming Hong and Yang, {Pan Chyr}",
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Chao, YC, Pan, SH, Yang, SC, Yu, SL, Che, TF, Lin, CW, Tsai, MS, Chang, GC, Wu, CH, Wu, YY, Lee, YC, Hong, T-M & Yang, PC 2009, 'Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma', American Journal of Respiratory and Critical Care Medicine, vol. 179, no. 2, pp. 123-133. https://doi.org/10.1164/rccm.200803-456OC

Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma. / Chao, Yu Chih; Pan, Szu Hua; Yang, Shuenn Chen; Yu, Sung Liang; Che, Ting Fang; Lin, Chung Wu; Tsai, Mu Shiun; Chang, Gee Chen; Wu, Che Hsiang; Wu, Yi Ying; Lee, Yung Chie; Hong, Tse-Ming; Yang, Pan Chyr.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 179, No. 2, 15.01.2009, p. 123-133.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma

AU - Chao, Yu Chih

AU - Pan, Szu Hua

AU - Yang, Shuenn Chen

AU - Yu, Sung Liang

AU - Che, Ting Fang

AU - Lin, Chung Wu

AU - Tsai, Mu Shiun

AU - Chang, Gee Chen

AU - Wu, Che Hsiang

AU - Wu, Yi Ying

AU - Lee, Yung Chie

AU - Hong, Tse-Ming

AU - Yang, Pan Chyr

PY - 2009/1/15

Y1 - 2009/1/15

N2 - Rationale: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. Objectives: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. Methods: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. Measurements and Main Results: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-α], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. Conclusions: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.

AB - Rationale: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. Objectives: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. Methods: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. Measurements and Main Results: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-α], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. Conclusions: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.

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