首页|UBE2G2 inhibits vasculogenic mimicry and metastasis of uveal melanoma by promoting ubiquitination of LGALS3BP
UBE2G2 inhibits vasculogenic mimicry and metastasis of uveal melanoma by promoting ubiquitination of LGALS3BP
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Uveal melanoma(UM)poses a significant lethality,with approximately 50％of those developing metastases surviving less than one year.In the progression of UM,vasculogenic mimicry(VM)induced by hypoxia plays a pivotal role,which also partially explains the resistance of UM to anti-angiogenic therapies.Nevertheless,the crucial molecular mechanisms underlying VM in the progres-sion of UM remain unclear.We identified ubiquitin conjugating enzyme E2 G2(UBE2G2)as a critical suppressor through transcriptomic sequencing and metastasis correlation screening.In UM,hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly allevi-ated by its overexpression.Mechanistically,UBE2G2 directly binds to galectin 3 binding protein(LGALS3BP)and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38(TRIM38),facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue.Further-more,UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and re-programming the tumor microenvironment.Therefore,targeting intercellular and intracellular molecular mechanisms of the hypoxia-UBE2G2-LGALS3BP axis may contribute to developing various therapeu-tic strategies for UM.
UBE2G2Vasculogenic mimicryInvasion and metastasisUveal melanomaUbiquitinationTumor microenvironmentLGALS3BPHypoxia
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