The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2

Tian-Shun Tsai, Chew N. Wu, Kai Wen Hsu, Wan Jung Liao, Min Chieh Yang, Anna Fen Yau Li, An Ming Wang, Min Liang Kuo, Chin Wen Chi

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progression of gastric cancer. Herein, we sought to address whether Notch1 signal pathway is involved in the control of progression in gastric cancer. We found that expression of Notch ligand Jagged1 was correlated with aggressiveness of human gastric cancer. Patients with Jagged1 expression in gastric cancer tissues had a poor survival rate compared with those without Jagged1 expression. The Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promoted the colony-forming ability and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. Migration and invasion abilities of SC-M1 cells were enhanced by N1IC. Furthermore, N1IC and C promoter-binding factor 1 (CBF1) bound to cyclooxygenase-2 (COX-2) promoter and elevated COX-2 expression in SC-M1 cells through a CBF1-dependent manner. The colony-forming, migration, and invasion abilities enhanced by N1IC were suppressed in SC-M1 cells after treatment with the COX-2 inhibitor NS-398 or knockdown of COX-2. These cellular processes inhibited by Notch1 knockdown were restored by prostaglandin E2 or exogenous COX-2. Taken together, these results suggest that activation of Notch1 signal pathway promotes progression of gastric cancer, at least in part through COX-2.

Original languageEnglish
Pages (from-to)5039-5048
Number of pages10
JournalCancer Research
Volume69
Issue number12
DOIs
Publication statusPublished - Jun 15 2009

Fingerprint

Notch1 Receptor
Cyclooxygenase 2
Stomach Neoplasms
Signal Transduction
Stomach
Neoplasms
Cyclooxygenase 2 Inhibitors
Dinoprostone
Adenocarcinoma
Survival Rate
Ligands
Carcinoma
Therapeutics
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tsai, T-S., Wu, C. N., Hsu, K. W., Liao, W. J., Yang, M. C., Li, A. F. Y., ... Chi, C. W. (2009). The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Research, 69(12), 5039-5048. https://doi.org/10.1158/0008-5472.CAN-08-4021

The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. / Tsai, Tian-Shun; Wu, Chew N.; Hsu, Kai Wen; Liao, Wan Jung; Yang, Min Chieh; Li, Anna Fen Yau; Wang, An Ming; Kuo, Min Liang; Chi, Chin Wen.

In: Cancer Research, Vol. 69, No. 12, 15.06.2009, p. 5039-5048.

Research output: Contribution to journalArticle

Tsai, T-S, Wu, CN, Hsu, KW, Liao, WJ, Yang, MC, Li, AFY, Wang, AM, Kuo, ML & Chi, CW 2009, 'The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2', Cancer Research, vol. 69, no. 12, pp. 5039-5048. https://doi.org/10.1158/0008-5472.CAN-08-4021
Tsai, Tian-Shun ; Wu, Chew N. ; Hsu, Kai Wen ; Liao, Wan Jung ; Yang, Min Chieh ; Li, Anna Fen Yau ; Wang, An Ming ; Kuo, Min Liang ; Chi, Chin Wen. / The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. In: Cancer Research. 2009 ; Vol. 69, No. 12. pp. 5039-5048.
@article{5ce03da4edae41f8a002a93dd982d422,
title = "The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2",
abstract = "Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progression of gastric cancer. Herein, we sought to address whether Notch1 signal pathway is involved in the control of progression in gastric cancer. We found that expression of Notch ligand Jagged1 was correlated with aggressiveness of human gastric cancer. Patients with Jagged1 expression in gastric cancer tissues had a poor survival rate compared with those without Jagged1 expression. The Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promoted the colony-forming ability and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. Migration and invasion abilities of SC-M1 cells were enhanced by N1IC. Furthermore, N1IC and C promoter-binding factor 1 (CBF1) bound to cyclooxygenase-2 (COX-2) promoter and elevated COX-2 expression in SC-M1 cells through a CBF1-dependent manner. The colony-forming, migration, and invasion abilities enhanced by N1IC were suppressed in SC-M1 cells after treatment with the COX-2 inhibitor NS-398 or knockdown of COX-2. These cellular processes inhibited by Notch1 knockdown were restored by prostaglandin E2 or exogenous COX-2. Taken together, these results suggest that activation of Notch1 signal pathway promotes progression of gastric cancer, at least in part through COX-2.",
author = "Tian-Shun Tsai and Wu, {Chew N.} and Hsu, {Kai Wen} and Liao, {Wan Jung} and Yang, {Min Chieh} and Li, {Anna Fen Yau} and Wang, {An Ming} and Kuo, {Min Liang} and Chi, {Chin Wen}",
year = "2009",
month = "6",
day = "15",
doi = "10.1158/0008-5472.CAN-08-4021",
language = "English",
volume = "69",
pages = "5039--5048",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2

AU - Tsai, Tian-Shun

AU - Wu, Chew N.

AU - Hsu, Kai Wen

AU - Liao, Wan Jung

AU - Yang, Min Chieh

AU - Li, Anna Fen Yau

AU - Wang, An Ming

AU - Kuo, Min Liang

AU - Chi, Chin Wen

PY - 2009/6/15

Y1 - 2009/6/15

N2 - Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progression of gastric cancer. Herein, we sought to address whether Notch1 signal pathway is involved in the control of progression in gastric cancer. We found that expression of Notch ligand Jagged1 was correlated with aggressiveness of human gastric cancer. Patients with Jagged1 expression in gastric cancer tissues had a poor survival rate compared with those without Jagged1 expression. The Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promoted the colony-forming ability and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. Migration and invasion abilities of SC-M1 cells were enhanced by N1IC. Furthermore, N1IC and C promoter-binding factor 1 (CBF1) bound to cyclooxygenase-2 (COX-2) promoter and elevated COX-2 expression in SC-M1 cells through a CBF1-dependent manner. The colony-forming, migration, and invasion abilities enhanced by N1IC were suppressed in SC-M1 cells after treatment with the COX-2 inhibitor NS-398 or knockdown of COX-2. These cellular processes inhibited by Notch1 knockdown were restored by prostaglandin E2 or exogenous COX-2. Taken together, these results suggest that activation of Notch1 signal pathway promotes progression of gastric cancer, at least in part through COX-2.

AB - Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progression of gastric cancer. Herein, we sought to address whether Notch1 signal pathway is involved in the control of progression in gastric cancer. We found that expression of Notch ligand Jagged1 was correlated with aggressiveness of human gastric cancer. Patients with Jagged1 expression in gastric cancer tissues had a poor survival rate compared with those without Jagged1 expression. The Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promoted the colony-forming ability and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. Migration and invasion abilities of SC-M1 cells were enhanced by N1IC. Furthermore, N1IC and C promoter-binding factor 1 (CBF1) bound to cyclooxygenase-2 (COX-2) promoter and elevated COX-2 expression in SC-M1 cells through a CBF1-dependent manner. The colony-forming, migration, and invasion abilities enhanced by N1IC were suppressed in SC-M1 cells after treatment with the COX-2 inhibitor NS-398 or knockdown of COX-2. These cellular processes inhibited by Notch1 knockdown were restored by prostaglandin E2 or exogenous COX-2. Taken together, these results suggest that activation of Notch1 signal pathway promotes progression of gastric cancer, at least in part through COX-2.

UR - http://www.scopus.com/inward/record.url?scp=67449168389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67449168389&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-08-4021

DO - 10.1158/0008-5472.CAN-08-4021

M3 - Article

C2 - 19491270

AN - SCOPUS:67449168389

VL - 69

SP - 5039

EP - 5048

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 12

ER -