ArticleCell communication and signaling : CCS2021
Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 28 citations in OpenAlex.
- Article
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- Stiff matrix promotes lung cancer cell migration through down-regulating the Piezo1 channel expression to facilitate CaMaterials today. Bio · 2026Article
- Protective effect of compound K against podocyte injury in chronic kidney disease by maintaining mitochondrial homeostasis.Scientific reports · 2025Article
- Synthesis and in vitro evaluation of benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives as anticancer agents targeting the RhoA/ROCK pathway.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC.Journal of translational medicine · 2024Article
- CENPA knockdown restrains cell progression and tumor growth in breast cancer by reducing PLA2R1 promoter methylation and modulating PLA2R1/HHEX axis.Cellular and molecular life sciences : CMLS · 2024Article
- Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.Chinese journal of integrative medicine · 2024Article
- An artificial intelligence network-guided signature for predicting outcome and immunotherapy response in lung adenocarcinoma patients based on 26 machine learning algorithms.Cell proliferation · 2023Article
- CRISPR screens identify gene targets at breast cancer risk loci.Genome biology · 2023Article
- Dahuang-Taoren, a botanical drug combination, ameliorates adenomyosisFrontiers in pharmacology · 2023Article
- The combination of positive anti‑WDR1 antibodies with negative anti‑CFL1 antibodies in serum is a poor prognostic factor for patients with esophageal carcinoma.Medicine internationalArticle
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
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. Video abstract.
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