7/28/2023 0 Comments Affinity publisher spread columnsCD98 can promote the activation of β1 and β3 integrins by FAK phosphorylation, which eventually promotes cancer cell survival, proliferation and migration. CD98 was reported to be associated with basigin, contributing to tumor growth in a variety of cancers with a high expression level of this protein. Identifying the binding partners of basigin could help elucidate how basigin functions in cancer progression. Previously, we identified the downstream effectors of basigin, such as PI3K, TGF-β and MMPs, which can promote liver cancer phenotypes and behavior, but the precise mechanism remains obscure. Basigin, also known as CD147 or EMMPRIN (extracellular matrix metalloproteinase inducer), is gradually being recognized as a cancer-associated biomarker, and significant clinical therapeutic progress has been made using anti-basigin monoclonal antibodies that target HCC. HCC is a common malignancy worldwide, and to develop targeted diagnostic tools and novel therapies efforts have been tried to understand the molecular basis of HCC. Although the basic features of the endocytic process had been established more than two decades ago, researches on how the vesicles are recycled to mediate the distribution of tumor drivers, especially the CIE proteins, are rare. The recycling endosomes control the amplitude and duration of oncogenic signaling from cancerous cells by regulating receptor recycling and redistribution. Then, a series of sorting events affect the fate of the internalized proteins, resulting in either degradation in the lysosomes or recycling back to the plasma membrane. After endocytosis, the internalized proteins (both CME and CIE protein) first converge into Rab5a-positive endosomes. Caveolin, flotillin-1, RhoA and Arf6 were reported to mediate different types of CIE. Clathrin, adaptor proteins, dynamin and other GTPases participate in and regulate the process of CME. Membrane proteins could be internalized through CME (clathrin-mediated endocytosis) or CIE (clathrin-independent endocytosis). ĭysregulated endocytosis contributes significantly to several hallmarks of cancer. The aberrant distribution of membrane proteins, including immune adhesion molecules, conjunction proteins and many RTKs (receptor tyrosine kinases), can create markedly altered tissue polarity and instigate motile phenotypes and cancerous cell behavior in normal cells. Conclusionīasigin, as a redistribution chaperone of CD98, plays a critical role in promoting cell spreading and the progression of hepatocellular carcinoma. This recycling process for basigin and CD98 promotes cell spreading and tumor growth in liver cancer xenografts. Internalization of basigin and CD98 was flotillin-1 regulated the and their recycling was mediated by Arf6. Resultsīasigin and CD98 were highly expressed and co-localized on the human hepatocellular carcinoma (HCC) cell membrane basigin can directly bind to CD98, mediating CD98 redistribution on the HCC cell membrane and activating the downstream integrin signaling pathway. The role of CD98 was confirmed in liver cancer cells by cell spreading in vitro and tumorigenicity by nude mice xenograft tumor assay in vivo membrane expression of basigin and CD98 in SMMC-7721 was measured by FCAS pull down and SPR analysis were uses to reveal the direct association between basigin and CD98 DsRed1 tagged CD98 was blocked in the cytoplasm in K7721 (whose basigin was knockn out) and had a well colocalization with ER and Rab5a positive recycling endosomes under co-focal finally, by FRET imaging and FCAS we observed the internalization of basigin and CD98 was flotillin-1-regulated, and their recycle at early steps was Arf6-mediated. The endocytosis and recyle of basigin and CD98 might play critical roles in cancer. CD98 promotes cell spreading and tumorigenicity by triggering integrin clustering and enhancing cell adhesion to the extracellular matrix. Basigin can enhance cancer progression, but its precise mechanism remains unclear. Dysregulated endocytosis of membrane proteins contributes significantly to several hallmarks of cancer.
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