title: Interleukin-8 promotes cell migration through integrin αvβ6 upregulation in colorectal cancer.
abstract: Colorectal cancer (CRC), which is notorious for high morbidity and mortality around the world, shows a predilection for metastasis to liver. Interleukin-8 (IL-8), a chemokine with a defining CXC amino acid motif, has been reported to promote CRC cell migration and is associated with poor prognosis of CRC. However, the underlying molecular mechanism of IL-8-mediated migration remains obscure. In this study, we first demonstrated the cross talk between IL-8 and integrin αvβ6. We analyzed 139 human CRC samples, and found that the immunohistochemical expression of αvβ6 was significantly correlated with expression of IL-8. Furthermore, IL-8 increased the migration through integrin αvβ6 in human CRC cells, and both CXCR1 and CXCR2 were primarily involved during the process. IL-8 upregulated αvβ6 expression in a dose-dependent manner through activation of ERK and Ets-1 signaling pathway. Taken together, our results indicated that IL-8 enhances the migration of CRC cells by increasing αvβ6 integrin expression through the ERK/Ets-1 pathway. Targeting integrin αvβ6 in IL-8 expressing tumors might be a potential therapeutic strategy for CRC patients.
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Fengkai
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong, China.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Enyu
authors.initials: E
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Benjia
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Zhengchuan
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China. Electronic address: jun_niujun@outlook.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Niu
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C494041:ETS1 protein, human; D016023:Integrins; D016209:Interleukin-8; D050784:Proto-Oncogene Protein c-ets-1; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins; C073878:integrin alphavbeta6
keywords: Colorectal cancer; Integrin αvβ6; Interleukin-8; Migration