Ethanol enhances the interaction of breast cancer cells over-expressing erbB2 with fibronectin

Mei Xu, Kimberly A. Bower, Gang Chen, Xianglin Shi, Zheng Dong, Zunji Ke, Jia Luo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. However, the underlying ellular/molecular mechanisms remain unknown. Amplification of ErbB2 or HER2, a receptor tyrosine kinase of the ErbB family, is found in 20 to 30% of patients with breast cancer. We have previously demonstrated that the effect of ethanol on the migration/invasion of breast cancer cells positively correlated with the expression levels of ErbB2. Adhesion to the extracellular matrix (ECM) is an important initial step for cancer cell invasion and metastasis. In this study, we investigated the effects of ethanol on the adhesion of MCF7 breast cancer cells over-expressing ErbB2 (MCF7 ErbB2) to human plasma fibronectin. Methods: To test the hypothesis that ethanol may enhance the attachment of human breast cancer cells to fibronectin, an important component of the ECM, we evaluated the effect of ethanol on the expression of focal adhesions, cell attachment, and ErbB2 signaling in cultured MCF7ErbB2 cells. Results: Exposure to ethanol drastically enhanced the adhesion of MCFErbB2 cells to fibronectin and increased the expression of focal adhesions. Ethanol induced phosphorylation of ErbB2 at Tyr1248, FAK at Tyr861, and cSrc at Try216. Ethanol promoted the interaction among ErbB2, FAK, and cSrc, and the formation of a focal complex. AG825, a selective ErbB2 inhibitor, attenuated the ethanol-induced phosphorylation of ErbB2 and its association with FAK. Furthermore, AG825 blocked ethanol-promoted cell/fibronectin adhesion as well as the expression of focal adhesions. Conclusions: Our results suggest that ethanol enhances the adhesion of breast cancer cells to fibronectin in an ErbB2-dependent manner, and the FAK pathway plays an important role in ethanol-induced formation of a focal complex.

Original languageEnglish (US)
Pages (from-to)751-760
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume34
Issue number5
DOIs
StatePublished - May 1 2010

Fingerprint

Fibronectins
Ethanol
Cells
Breast Neoplasms
Adhesion
Focal Adhesions
Phosphorylation
Cell adhesion
Cell Adhesion
Extracellular Matrix
Neoplasm Metastasis
Plasma (human)
Receptor Protein-Tyrosine Kinases
Carcinogens
Amplification
Cultured Cells
Association reactions

Keywords

  • Alcohol
  • Focal Adhesion
  • Metastasis
  • Migration
  • Tumorigenesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Ethanol enhances the interaction of breast cancer cells over-expressing erbB2 with fibronectin. / Xu, Mei; Bower, Kimberly A.; Chen, Gang; Shi, Xianglin; Dong, Zheng; Ke, Zunji; Luo, Jia.

In: Alcoholism: Clinical and Experimental Research, Vol. 34, No. 5, 01.05.2010, p. 751-760.

Research output: Contribution to journalArticle

Xu, Mei ; Bower, Kimberly A. ; Chen, Gang ; Shi, Xianglin ; Dong, Zheng ; Ke, Zunji ; Luo, Jia. / Ethanol enhances the interaction of breast cancer cells over-expressing erbB2 with fibronectin. In: Alcoholism: Clinical and Experimental Research. 2010 ; Vol. 34, No. 5. pp. 751-760.
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T1 - Ethanol enhances the interaction of breast cancer cells over-expressing erbB2 with fibronectin

AU - Xu, Mei

AU - Bower, Kimberly A.

AU - Chen, Gang

AU - Shi, Xianglin

AU - Dong, Zheng

AU - Ke, Zunji

AU - Luo, Jia

PY - 2010/5/1

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N2 - Background: Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. However, the underlying ellular/molecular mechanisms remain unknown. Amplification of ErbB2 or HER2, a receptor tyrosine kinase of the ErbB family, is found in 20 to 30% of patients with breast cancer. We have previously demonstrated that the effect of ethanol on the migration/invasion of breast cancer cells positively correlated with the expression levels of ErbB2. Adhesion to the extracellular matrix (ECM) is an important initial step for cancer cell invasion and metastasis. In this study, we investigated the effects of ethanol on the adhesion of MCF7 breast cancer cells over-expressing ErbB2 (MCF7 ErbB2) to human plasma fibronectin. Methods: To test the hypothesis that ethanol may enhance the attachment of human breast cancer cells to fibronectin, an important component of the ECM, we evaluated the effect of ethanol on the expression of focal adhesions, cell attachment, and ErbB2 signaling in cultured MCF7ErbB2 cells. Results: Exposure to ethanol drastically enhanced the adhesion of MCFErbB2 cells to fibronectin and increased the expression of focal adhesions. Ethanol induced phosphorylation of ErbB2 at Tyr1248, FAK at Tyr861, and cSrc at Try216. Ethanol promoted the interaction among ErbB2, FAK, and cSrc, and the formation of a focal complex. AG825, a selective ErbB2 inhibitor, attenuated the ethanol-induced phosphorylation of ErbB2 and its association with FAK. Furthermore, AG825 blocked ethanol-promoted cell/fibronectin adhesion as well as the expression of focal adhesions. Conclusions: Our results suggest that ethanol enhances the adhesion of breast cancer cells to fibronectin in an ErbB2-dependent manner, and the FAK pathway plays an important role in ethanol-induced formation of a focal complex.

AB - Background: Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. However, the underlying ellular/molecular mechanisms remain unknown. Amplification of ErbB2 or HER2, a receptor tyrosine kinase of the ErbB family, is found in 20 to 30% of patients with breast cancer. We have previously demonstrated that the effect of ethanol on the migration/invasion of breast cancer cells positively correlated with the expression levels of ErbB2. Adhesion to the extracellular matrix (ECM) is an important initial step for cancer cell invasion and metastasis. In this study, we investigated the effects of ethanol on the adhesion of MCF7 breast cancer cells over-expressing ErbB2 (MCF7 ErbB2) to human plasma fibronectin. Methods: To test the hypothesis that ethanol may enhance the attachment of human breast cancer cells to fibronectin, an important component of the ECM, we evaluated the effect of ethanol on the expression of focal adhesions, cell attachment, and ErbB2 signaling in cultured MCF7ErbB2 cells. Results: Exposure to ethanol drastically enhanced the adhesion of MCFErbB2 cells to fibronectin and increased the expression of focal adhesions. Ethanol induced phosphorylation of ErbB2 at Tyr1248, FAK at Tyr861, and cSrc at Try216. Ethanol promoted the interaction among ErbB2, FAK, and cSrc, and the formation of a focal complex. AG825, a selective ErbB2 inhibitor, attenuated the ethanol-induced phosphorylation of ErbB2 and its association with FAK. Furthermore, AG825 blocked ethanol-promoted cell/fibronectin adhesion as well as the expression of focal adhesions. Conclusions: Our results suggest that ethanol enhances the adhesion of breast cancer cells to fibronectin in an ErbB2-dependent manner, and the FAK pathway plays an important role in ethanol-induced formation of a focal complex.

KW - Alcohol

KW - Focal Adhesion

KW - Metastasis

KW - Migration

KW - Tumorigenesis

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