Author: Wang, Xiang; Wei, Xiaofan; Yuan, Yang; Sun, Qingrui; Zhan, Jun; Zhang, Jing; Tang, Yan; Li, Feng; Ding, Lihua; Ye, Qinong; Zhang, Hongquan
Description: FHL1 has been recognized for a long time as a tumor suppressor protein that associates with both the actin cytoskeleton and the transcriptional machinery. We present in this study a paradigm that phosphorylated FHL1 functions as an oncogenic protein by promoting tumor cell proliferation. The cytosolic tyrosine kinase Src interacts with and phosphorylates FHL1 at Y149 and Y272, which switches FHL1 from a tumor suppressor to a cell growth accelerator. Phosphorylated FHL1 translocates into the nucleus, where it binds to the transcription factor BCLAF1 and promotes tumor cell growth. Importantly, the phosphorylation of FHL1 is increased in tissues from lung adenocarcinoma patients despite the down-regulation of total FHL1 expression. Kindlin-2 was found to interact with FHL1 and recruit FHL1 to focal adhesions. Kindlin-2 competes with Src for binding to FHL1 and suppresses Src-mediated FHL1 phosphorylation. Collectively, we demonstrate that FHL1 can either suppress or promote tumor cell growth depending on the status of the sites for phosphorylation by Src.
Subject headings: Active Transport; Cell Nucleus; Adenocarcinoma of Lung, enzymology, genetics, pathology; Animals; Binding; Competitive; Cell Movement; Cell Proliferation; Female; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins, metabolism; LIM Domain Proteins, metabolism; Lung Neoplasms, pathology; Membrane Proteins, metabolism; Mice; Inbred BALB C; Mice, Nude; Muscle Proteins, metabolism; Neoplasm Invasiveness; Neoplasm Proteins, metabolism; Phosphorylation; Protein Binding; Repressor Proteins, metabolism; Signal Transduction; Time Factors; Tumor Burden; Tumor Suppressor Proteins, metabolism; Uterine Cervical Neoplasms, pathology; src-Family Kinases, metabolism
Publication year: 2018
Journal or book title: The Journal of cell biology
Volume: 217
Issue: 4
Pages: 1335-1351
Find the full text: https://www.strategian.com/fulltext/Wang2018a.pdf
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Serial number: 3687