ULK1 phosphorylates Exo70 to suppress breast cancer metastasis
| Autor: | Xinquan Wang, Wei Guo, Xiaoting Hong, Bin Wu, Li Xiao, Ravi Radhakrishnan, Kunrong Mei, Qiang Yu, Linhai Zhong, Jingzhou Xiang, Yan-yan Zhan, Panying Mi, Liang Xu, Cao Hanwei, Binbin Chen, Wenqing Zhang, Liyuan Mao, Tianhui Hu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell biology Science medicine.medical_treatment Cell Vesicular Transport Proteins General Physics and Astronomy Mice Nude Exocyst Breast Neoplasms Matrix metalloproteinase Biochemistry General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor medicine Animals Autophagy-Related Protein-1 Homolog Humans Secretion Neoplasm Metastasis Phosphorylation lcsh:Science Protein kinase A Cancer Multidisciplinary Chemistry Growth factor Intracellular Signaling Peptides and Proteins General Chemistry 3. Good health Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell Cancer research lcsh:Q Female |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2041-1723 |
| Popis: | 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. Elevated expression of ULK1 is known to be inversely correlated with breast cancer metastasis. Here, the authors report Exo70 as a substrate of ULK1 that suppresses cancer metastasis, and show that ERK1/2 mediated phosphorylation of Exo70 leads to opposing effects on tumour cell invasion. |
| Databáze: | OpenAIRE |
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