Disruption of lysosome function promotes tumor growth and metastasis in Drosophila.

Journal Article

Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradation pathway components contribute to tumor development and progression. Loss-of-function mutations in the Class C vacuolar protein sorting (VPS) gene, deep orange (dor), dramatically promote tumor overgrowth and invasion of the Ras(V12) cells. Knocking down either of the two other components of the Class C VPS complex, carnation (car) and vps16A, also renders Ras(V12) cells capable for uncontrolled growth and metastatic behavior. Finally, chemical disruption of the lysosomal function by feeding animals with antimalarial drugs, chloroquine or monensin, leads to malignant tumor growth of the Ras(V12) cells. Taken together, our data provide evidence for a causative role of lysosome dysfunction in tumor growth and invasion and indicate that members of the Class C VPS complex behave as tumor suppressors.

Full Text

Duke Authors

Cited Authors

  • Chi, C; Zhu, H; Han, M; Zhuang, Y; Wu, X; Xu, T

Published Date

  • July 9, 2010

Published In

Volume / Issue

  • 285 / 28

Start / End Page

  • 21817 - 21823

PubMed ID

  • 20418542

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M110.131714

Language

  • eng

Conference Location

  • United States