Abstract

Objective: To study the mechanism of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK)-enhanced migration of colon cancer cells. BACKGROUND DATA:: Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco-specific carcinogen, NNK, was reported to increase DNA synthesis of colon cancer cells. Since metastasis is the major cause of cancer death, the influence of NNK on the migration of colon cancer cells remains to be determined. METHODS:: Receptor for NNK in colon cancer cells was identified by polymerase chain reaction (PCR) and real-time PCR. The influence of NNK on migration of colon cancer cells was evaluated by transwell and wound-healing assay. Receptor-mediated migration was studied by both inhibitor and small interfering RNA. RESULTS:: α7 nicotinic acetylcholine receptor, α7-nAChR, was identified in 2 colon cancer cell lines, HT29 and DLD-1. NNK enhanced HT29 cell migration in both transwell and wound-healing assays. NNK also enhanced DLD-1 cell migration in dose dependent manner. We used inhibitor and siRNA to demonstrate that α7-nAChR mediated NNK-enhanced colon cancer cell migration and downregulation of E-cadherin were involved in NNK-enhanced migration of colon cancer cells. Furthermore, Snail and ZEB1, 2 major transcription repressors of E-cadherin in colon cancers, were induced by NNK treatment. CONCLUSIONS:: Tobacco specific carcinogen, NNK, enhanced colon cancer metastasis through α7-nAChR and E-cadherin-one of the hallmarks of epithelial mesenchymal transition-and its transcription repressors. Therefore, smoking should be avoided in the patients with colorectal cancer.

Original languageEnglish
Pages (from-to)978-985
Number of pages8
JournalAnnals of Surgery
Volume249
Issue number6
DOIs
Publication statusPublished - Jun 2009

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Nicotinic Receptors
Carcinogens
Colonic Neoplasms
Tobacco
Cell Movement
Cadherins
Wound Healing
Small Interfering RNA
Colorectal Neoplasms
Smoking
Neoplasm Metastasis
HT29 Cells
Epithelial-Mesenchymal Transition
Real-Time Polymerase Chain Reaction
Cause of Death
Down-Regulation
Cell Line
Polymerase Chain Reaction
Mortality
DNA

ASJC Scopus subject areas

  • Surgery

Cite this

@article{83baa53723194943b0c99c64860d9719,
title = "Tobacco-specific carcinogen enhances colon cancer cell migration through α7-nicotinic acetylcholine receptor",
abstract = "Objective: To study the mechanism of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK)-enhanced migration of colon cancer cells. BACKGROUND DATA:: Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco-specific carcinogen, NNK, was reported to increase DNA synthesis of colon cancer cells. Since metastasis is the major cause of cancer death, the influence of NNK on the migration of colon cancer cells remains to be determined. METHODS:: Receptor for NNK in colon cancer cells was identified by polymerase chain reaction (PCR) and real-time PCR. The influence of NNK on migration of colon cancer cells was evaluated by transwell and wound-healing assay. Receptor-mediated migration was studied by both inhibitor and small interfering RNA. RESULTS:: α7 nicotinic acetylcholine receptor, α7-nAChR, was identified in 2 colon cancer cell lines, HT29 and DLD-1. NNK enhanced HT29 cell migration in both transwell and wound-healing assays. NNK also enhanced DLD-1 cell migration in dose dependent manner. We used inhibitor and siRNA to demonstrate that α7-nAChR mediated NNK-enhanced colon cancer cell migration and downregulation of E-cadherin were involved in NNK-enhanced migration of colon cancer cells. Furthermore, Snail and ZEB1, 2 major transcription repressors of E-cadherin in colon cancers, were induced by NNK treatment. CONCLUSIONS:: Tobacco specific carcinogen, NNK, enhanced colon cancer metastasis through α7-nAChR and E-cadherin-one of the hallmarks of epithelial mesenchymal transition-and its transcription repressors. Therefore, smoking should be avoided in the patients with colorectal cancer.",
author = "Wei, {Po Li} and Chang, {Yu Jia} and Ho, {Yuan Soon} and Lee, {Chia Hwa} and Yang, {Yi Yuan} and Jane An and Lin, {Shyr Yi}",
year = "2009",
month = "6",
doi = "10.1097/SLA.0b013e3181a6ce7e",
language = "English",
volume = "249",
pages = "978--985",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
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TY - JOUR

T1 - Tobacco-specific carcinogen enhances colon cancer cell migration through α7-nicotinic acetylcholine receptor

AU - Wei, Po Li

AU - Chang, Yu Jia

AU - Ho, Yuan Soon

AU - Lee, Chia Hwa

AU - Yang, Yi Yuan

AU - An, Jane

AU - Lin, Shyr Yi

PY - 2009/6

Y1 - 2009/6

N2 - Objective: To study the mechanism of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK)-enhanced migration of colon cancer cells. BACKGROUND DATA:: Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco-specific carcinogen, NNK, was reported to increase DNA synthesis of colon cancer cells. Since metastasis is the major cause of cancer death, the influence of NNK on the migration of colon cancer cells remains to be determined. METHODS:: Receptor for NNK in colon cancer cells was identified by polymerase chain reaction (PCR) and real-time PCR. The influence of NNK on migration of colon cancer cells was evaluated by transwell and wound-healing assay. Receptor-mediated migration was studied by both inhibitor and small interfering RNA. RESULTS:: α7 nicotinic acetylcholine receptor, α7-nAChR, was identified in 2 colon cancer cell lines, HT29 and DLD-1. NNK enhanced HT29 cell migration in both transwell and wound-healing assays. NNK also enhanced DLD-1 cell migration in dose dependent manner. We used inhibitor and siRNA to demonstrate that α7-nAChR mediated NNK-enhanced colon cancer cell migration and downregulation of E-cadherin were involved in NNK-enhanced migration of colon cancer cells. Furthermore, Snail and ZEB1, 2 major transcription repressors of E-cadherin in colon cancers, were induced by NNK treatment. CONCLUSIONS:: Tobacco specific carcinogen, NNK, enhanced colon cancer metastasis through α7-nAChR and E-cadherin-one of the hallmarks of epithelial mesenchymal transition-and its transcription repressors. Therefore, smoking should be avoided in the patients with colorectal cancer.

AB - Objective: To study the mechanism of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK)-enhanced migration of colon cancer cells. BACKGROUND DATA:: Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco-specific carcinogen, NNK, was reported to increase DNA synthesis of colon cancer cells. Since metastasis is the major cause of cancer death, the influence of NNK on the migration of colon cancer cells remains to be determined. METHODS:: Receptor for NNK in colon cancer cells was identified by polymerase chain reaction (PCR) and real-time PCR. The influence of NNK on migration of colon cancer cells was evaluated by transwell and wound-healing assay. Receptor-mediated migration was studied by both inhibitor and small interfering RNA. RESULTS:: α7 nicotinic acetylcholine receptor, α7-nAChR, was identified in 2 colon cancer cell lines, HT29 and DLD-1. NNK enhanced HT29 cell migration in both transwell and wound-healing assays. NNK also enhanced DLD-1 cell migration in dose dependent manner. We used inhibitor and siRNA to demonstrate that α7-nAChR mediated NNK-enhanced colon cancer cell migration and downregulation of E-cadherin were involved in NNK-enhanced migration of colon cancer cells. Furthermore, Snail and ZEB1, 2 major transcription repressors of E-cadherin in colon cancers, were induced by NNK treatment. CONCLUSIONS:: Tobacco specific carcinogen, NNK, enhanced colon cancer metastasis through α7-nAChR and E-cadherin-one of the hallmarks of epithelial mesenchymal transition-and its transcription repressors. Therefore, smoking should be avoided in the patients with colorectal cancer.

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U2 - 10.1097/SLA.0b013e3181a6ce7e

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VL - 249

SP - 978

EP - 985

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 6

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