biostudies-literatureOgura YNational Heart, Lung, and Blood InstituteMinistry of Education, Culture, Sports, Science and TechnologyUniversity of TsukubaNational Institutes of Health102335https://www.ebi.ac.uk/biostudies/studies/S-EPMC9440431biostudies-literatureUnknown298(9)Disordered expression and distribution of plasma membrane proteins at the cell surface leads to diverse malignant phenotypes in tumors, including cell invasion. The ubiquitin-specific protease TRE17/USP6, an oncogene identified in Ewing sarcoma, is highly expressed in several cancers and locally aggressive tumor-like lesions. We have previously demonstrated that TRE17 regulates the trafficking of plasma membrane proteins that enter cells via clathrin-independent endocytosis (CIE); TRE17 prevents CIE cargo proteins from being targeted to lysosomes for degradation by deubiquitylating them. However, functional insights into the effects of TRE17-mediated CIE cargo trafficking on cell invasion remain unknown. Here, we show that increased expression of TRE17 enhances invasiveness of the human saThe Journal of biological chemistryUbiquitin-specific protease TRE17/USP6 promotes tumor cell invasion through the regulation of glycoprotein CD147 intracellular trafficking.PMC9440431HT-108021K0614617K0732722K0619918H02601CD14719K06653Ogura YKawaguchi AKanaho YOhbayashi NFunakoshi YfalseUbiquitin-specific protease TRE17/USP6 promotes tumor cell invasion through the regulation of glycoprotein CD147 intracellular trafficking.Disordered expression and distribution of plasma membrane proteins at the cell surface leads to diverse malignant phenotypes in tumors, including cell invasion. The ubiquitin-specific protease TRE17/USP6, an oncogene identified in Ewing sarcoma, is highly expressed in several cancers and locally aggressive tumor-like lesions. We have previously demonstrated that TRE17 regulates the trafficking of plasma membrane proteins that enter cells via clathrin-independent endocytosis (CIE); TRE17 prevents CIE cargo proteins from being targeted to lysosomes for degradation by deubiquitylating them. However, functional insights into the effects of TRE17-mediated CIE cargo trafficking on cell invasion remain unknown. Here, we show that increased expression of TRE17 enhances invasiveness of the human sa2022-01-01T00:00:00Z2022 Sep2025-04-20T00:42:54.937Z2025-04-20T00:42:54.937ZS-EPMC94404313592670710.1016/j.jbc.2022.102335