Sialylation of vesicular integrin β1 of bladder cancer cells promotes its binding to fibronectin, and endocytic entry of small extracellular vesicles into recipient epithelial cells

ABSTRACT: Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles. However, functions in sEV of sialic acids, the terminal component of glycoconjugates, are poorly understood. We observed greatly increased sialic acid levels in sEV from bladder cancer cells. These sEV promoted the oncogenic transformation of recipient normal bladder epithelial cells. When sialic acids on sEV were eliminated, sEV uptake by recipient cells was significantly reduced. Sialylation of vesicular integrin β1 was found to play a key role in sEV uptake. Desialylation downstream of the hybrid domain of vesicular integrin β1 inhibited its binding to matrix fibronectin, reduced sEV entry into recipient cells, and suppressed metastasis of those cells. Our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bladder Cell, Cell Culture

DISEASE(S): Bladder Transitional Cell Carcinoma

SUBMITTER: Meixuan Lin  

LAB HEAD: Feng Guan

PROVIDER: PXD036973 | Pride | 2024-05-21

REPOSITORIES: Pride