Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells

Cell Communication and Signaling

Guilin Ma¹  Yingying Wang¹  Wenjie Guo¹  Xiaopeng Li¹  Ning Mu¹  Xiangguo Liu²  Ling Su² 

[1] Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Room N8-110, 72 Binhai Road, 266237, Qingdao, China;Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Room N8-110, 72 Binhai Road, 266237, Qingdao, China;Shandong Provincial Collaborative Innovation Center of Cell Biology, School of Life Sciences, Shandong Normal University, Jinan, China;

关键词: Hhex;    RHOA;    CDC42;    RHOGDIA;    p-CFL1;   

DOI  :  10.1186/s12964-021-00763-6

来源: Springer

【 摘 要 】

BackgroundHhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior–posterior axis formation, vascular development and HSCs self-renewal etc. Hhex is linked to many diseases such as cancers, leukemia, and type-2 diabetes. Although Hhex is reported to inhibit cell migration and invasion of breast and prostate epithelial cells by upregulating Endoglin expression, the effect and molecular mechanism for lung cancer cell motility regulation remains elusive.MethodsHuman non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of Hhex regulating lung cancer cell migration by using Western blot, immunoprecipitation, wound-healing scratch assay, laser confocal.ResultsOur data indicated that Hhex could inhibit cell migration and cell protrusion formation in lung cancer cells. In addition, Hhex inhibited CFL1 phosphorylation to keep its F-actin-severing activity. RHOGDIA was involved in Hhex-induced CFL1 phosphorylation regulation. Hhex enhanced RHOGDIA interaction with RHOA/CDC42, thus maintaining RHOA/CDC42 at an inactive form.ConclusionCollectively, these data indicate that Hhex inhibited the activation of RHOA/CDC42 by enhancing interaction of RHOGDIA with RHOA/CDC42, and then RHOA/ CDC42-p-CFL1 signaling pathway was blocked. Consequently, the formation of Filopodium and Lamellipodium on the cell surface was suppressed, and thus the ability of lung cancer cells to migrate was decreased accordingly. Our findings show Hhex plays an important role in regulating migration of lung cancer cells and may provide a potential target for lung cancer therapy.FSYn6j34J4ZMCghGVb9zTbVideo abstract

【 授权许可】

CC BY