Exo70 Enhances Exosome Secretion by Modulating Multivesicular Body Trafficking to Promote Pancreatic Cancer Metastasis
10.3971/j.issn.1000-8578.2025.25.0232
- VernacularTitle:Exo70通过调控多泡体转运增强外泌体分泌促进胰腺癌细胞的转移
- Author:
Wenqing ZHANG
1
;
Jingzhou XIANG
2
;
Tianhui HU
1
Author Information
1. Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China.
2. Oncology Department, Wuhan Asia General Hospital, Wuhan 430050, China.
- Publication Type:BASICRESEARCH
- Keywords:
Exo70;
Pancreatic cancer;
Exosomes;
Metastasis
- From:
Cancer Research on Prevention and Treatment
2025;52(7):585-591
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and molecular mechanisms of Exo70 in the metastasis of pancreatic cancer cells. Methods Stable cell lines with Exo70 knockdown or overexpression were established using lentiviral infection. The migration ability of pancreatic cancer cells was assessed by Transwell assay. The morphology, particle size, and secretion levels of exosomes were observed using transmission electron microscopy. Changes in the expression of Exo70 and exosomal marker proteins were detected by Western blot. The localization of multivesicular bodies (MVBs) was examined by immunofluorescence. Results Exo70 knockdown inhibited the migration ability of pancreatic cancer cells and substantially reduced the total amount of exosome secretion. By contrast, Exo70 overexpression enhanced the migration ability of pancreatic cancer cells. Immunofluorescence results showed that Exo70 knockdown induced the perinuclear accumulation of CD63 and LAMP2, leading to an increase in MVB accumulation and lysosomal degradation in pancreatic cancer cells. Conclusion Exo70 promotes the normal transport of MVBs and maintains exosome secretion. Its knockdown enhances the lysosomal degradation of MVBs, resulting in impaired exosome biogenesis and secretion and thereby inhibiting the migration of pancreatic cancer cells.