ULK1 phosphorylates Exo70 to suppress breast cancer metastasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31913283.
- Also identified by DOI 10.1038/s41467-019-13923-7 and PMC identifier 6949295.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Increased expression of protein kinase ULK1 was reported to negatively correlate with breast cancer metastasis. Here we report that ULK1 suppresses the migration and invasion of human breast cancer cells. The suppressive effect is mediated through direct phosphorylation of Exo70, a key component of the exocyst complex. ULK1 phosphorylation inhibits Exo70 homo-oligomerization as well as its assembly to the exocyst complex, which are needed for cell protrusion formation and matrix metalloproteinases secretion during cell invasion. Reversely, upon growth factor stimulation, Exo70 is phosphorylated by ERK1/2, which in turn suppresses its phosphorylation by ULK1. Together, our study identifies Exo70 as a substrate of ULK1 that inhibits cancer metastasis, and demonstrates that two counteractive regulatory mechanisms are well orchestrated during tumor cell invasion.
Medical subject headings
- Autophagy-Related Protein-1 Homolog
- Breast Neoplasms
- Intracellular Signaling Peptides and Proteins
- Vesicular Transport Proteins