KLF5 promotes cell migration by up-regulating FYN in bladder cancer cells

Chong Du; Yang Gao; Shan Xu; Jing Jia; Zhixin Huang; Jinhai Fan; Xinyang Wang; Dalin He; Peng Guo

doi:10.1002/1873-3468.12069

KLF5 promotes cell migration by up-regulating FYN in bladder cancer cells

FEBS Lett. 2016 Feb;590(3):408-18. doi: 10.1002/1873-3468.12069. Epub 2016 Feb 1.

Authors

Chong Du¹, Yang Gao¹, Shan Xu^{1

2}, Jing Jia¹, Zhixin Huang¹, Jinhai Fan^{1

2}, Xinyang Wang^{1

2}, Dalin He^{1

2}, Peng Guo^{1

2}

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China.
² Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.

PMID: 26786295
DOI: 10.1002/1873-3468.12069

Abstract

Krüppel-like factor 5 (KLF5) promotes cell proliferation of bladder cancer. However, whether KLF5 regulates other cell processes in bladder cancer is not clear. We found that KLF5 increases cell migration and lamellipodia formation, expression of FYN and phosphorylation of FAK in bladder cancer cells. In addition, KLF5 promotes transcription of FYN through binding to its promoter. FYN overexpression rescues cell migration and lamellipodia formation reduced by KLF5 knockdown. Furthermore, the KLF5/FYN/p-FAK axis is necessary for lysophosphatidic acid (LPA) to promote cell migration. Our findings indicate that both KLF5 and FYN are important in the regulation of cell migration in bladder cancer cells. We propose the KLF5/FYN/p-FAK axis as a potential therapeutic target in bladder cancer.

Keywords: FAK; FYN; KLF5; bladder cancer; cell migration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
Focal Adhesion Kinase 1 / metabolism*
Gene Expression Regulation, Neoplastic*
Humans
Kruppel-Like Transcription Factors / antagonists & inhibitors
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism*
Lysophospholipids / metabolism
Microscopy, Confocal
Microscopy, Fluorescence
Microscopy, Video
Neoplasm Proteins / agonists
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Phosphorylation
Promoter Regions, Genetic
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-fyn / agonists*
Proto-Oncogene Proteins c-fyn / genetics
Proto-Oncogene Proteins c-fyn / metabolism
Pseudopodia / metabolism*
Pseudopodia / pathology
RNA Interference
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Up-Regulation
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / pathology

Substances

KLF5 protein, human
Kruppel-Like Transcription Factors
Lysophospholipids
Neoplasm Proteins
Recombinant Proteins
FYN protein, human
Focal Adhesion Kinase 1
PTK2 protein, human
Proto-Oncogene Proteins c-fyn
lysophosphatidic acid