ArticleEBioMedicine2018
Human rhomboid family-1 modulates clathrin coated vesicle-dependent pro-transforming growth factor α membrane trafficking to promote breast cancer progression.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 34 citations in OpenAlex.
- The pancreatitis-cancer transformation-related factor, human rhomboid family-1, promotes pancreatic cancer progression through the SRC/YAP signaling pathway.Translational oncology · 2025Article
- Perturbation of mammary epithelial cell apicobasal polarity by RHBDF1-facilitated nuclear translocation of PKCζ.Biological research · 2024Article
- RHBDF1 modulates cisplatin sensitivity of small cell lung cancer through YAP1/Smad2 signaling pathway.Heliyon · 2024Article
- Pentapeptide PYRAE triggers ER stress-mediated apoptosis of breast cancer cells in mice by targeting RHBDF1-BiP interaction.Acta pharmacologica Sinica · 2024Article
- Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls.Proteomes · 2022Article
- Alternative splicing of the human rhomboid family-1 gene RHBDF1 inhibits epidermal growth factor receptor activation.The Journal of biological chemistry · 2022Article
- Inactive rhomboid proteins RHBDF1 and RHBDF2 (iRhoms): a decade of research in murine models.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Review
- RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression.Cancer cell international · 2021Article
- Vesicular trafficking-related proteins as the potential therapeutic target for breast cancer.Protoplasma · 2020Review
- Association of iRhom1 and iRhom2 expression with prognosis in patients with cervical cancer and possible signaling pathways.Oncology reports · 2020Article
- Rhomboids and regulation of receptor tyrosine kinase ligands shedding.EBioMedicine · 2018Article
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9 authors at 1 institution in 1 country.
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Abstract
backgroundEpidermal growth factor receptor (EGFR) signalling is critical in epithelial cancer development. Human rhomboid family-1 (RHBDF1) facilitates the secretion of TGFα, an EGFR ligand, in breast cancer; however, the underlying mechanism remains unclear. We evaluated the role for RHBDF1 in clathrin-coated vesicle (CCV)-dependent pro-TGFα membrane trafficking in breast cancer cells upon stimulation by G-protein coupled receptor (GPCR) agonists.
methodsRHBDF1 was silenced in various breast cancer cells using shRNA. TGFα levels, subcellular localization, and secretion were evaluated using ELISA, immunofluorescent staining, and coimmunoprecipitation. Phosphorylation and expression of relevant proteins were measured by western blotting. RHBDF1-dependent cell viability and invasion were measured.
findingsRHBDF1 mediates GPCR agonist-induced EGFR phosphorylation by promoting TGFα secretion in various types of breast cancer cells. RHBDF1 not only mediates ADAM17-dependent shedding of TGFα, but is essential in membrane trafficking of pro-TGFα. RHBDF1 silencing results in blocking of clathrin uncoating from CCV, a crucial step for the plasma membrane release of pro-TGFα. Interaction of RHBDF1 with auxilin-2, a CCV protein, determines the recruitment of HSC70 to CCV to facilitate clathrin uncoating. RHBDF1 function is required for the proliferation and mobility of breast cancer cells upon stimulation by Sphingosine 1 Phosphate (S1P), a GPCR agonist. We demonstrate a significant correlation between RHBDF1 overexpression and EGFR activation in breast cancer tissues.
interpretationRHBDF1 is an indispensable component of the protein trafficking machinery involved in GPCR-mediated EGFR transactivation, and is an attractive therapeutic target for cancer. FUND: National Natural Science Foundation of China (81,672,740 to ZSZ, 81,272,356 and 81,330,029 to LYL).
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