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ULK1 phosphorylates Exo70 to suppress breast cancer metastasis

Author

Listed:
  • Liyuan Mao

    (Xiamen University)

  • Yan-yan Zhan

    (Xiamen University)

  • Bin Wu

    (University of Pennsylvania)

  • Qiang Yu

    (Xiamen University)

  • Liang Xu

    (Xiamen University)

  • Xiaoting Hong

    (Xiamen University)

  • Linhai Zhong

    (Xiamen University)

  • Panying Mi

    (Xiamen University)

  • Li Xiao

    (Xiamen University
    Zhongshan Hospital Affiliated to Xiamen University)

  • Xinquan Wang

    (Tsinghua University)

  • Hanwei Cao

    (Xiamen University)

  • Wenqing Zhang

    (Xiamen University)

  • Binbin Chen

    (Xiamen University)

  • Jingzhou Xiang

    (Xiamen University)

  • Kunrong Mei

    (Tianjin University)

  • Ravi Radhakrishnan

    (University of Pennsylvania)

  • Wei Guo

    (University of Pennsylvania)

  • Tianhui Hu

    (Xiamen University)

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.

Suggested Citation

  • Liyuan Mao & Yan-yan Zhan & Bin Wu & Qiang Yu & Liang Xu & Xiaoting Hong & Linhai Zhong & Panying Mi & Li Xiao & Xinquan Wang & Hanwei Cao & Wenqing Zhang & Binbin Chen & Jingzhou Xiang & Kunrong Mei , 2020. "ULK1 phosphorylates Exo70 to suppress breast cancer metastasis," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13923-7
    DOI: 10.1038/s41467-019-13923-7
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    Cited by:

    1. Penelope L. Lindsay & Sergey Ivanov & Nathan Pumplin & Xinchun Zhang & Maria J. Harrison, 2022. "Distinct ankyrin repeat subdomains control VAPYRIN locations and intracellular accommodation functions during arbuscular mycorrhizal symbiosis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Diana Saleiro & Jeremy Q. Wen & Ewa M. Kosciuczuk & Frank Eckerdt & Elspeth M. Beauchamp & Chidera V. Oku & Gavin T. Blyth & Mariafausta Fischietti & Liliana Ilut & Marco Colamonici & William Palivos , 2022. "Discovery of a signaling feedback circuit that defines interferon responses in myeloproliferative neoplasms," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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