2. Academic Validation
  3. LKB1 suppresses growth and promotes the internalization of EGFR through the PIKFYVE lipid kinase

LKB1 suppresses growth and promotes the internalization of EGFR through the PIKFYVE lipid kinase

  • bioRxiv. 2023 Oct 20:2023.10.19.563158. doi: 10.1101/2023.10.19.563158.
John R Ferrarone,  Jerin Thomas,  Arun M Unni,  Yuxiang Zheng,  Michal J Nagiec,  Eric E Gardner,  Oksana Mashadova,  Kate Li,  Nikos Koundouros,  Antonino Montalbano,  Meer Mustafa,  Lewis C Cantley,  John Blenis,  Neville E Sanjana,  Harold Varmus
PMID: 37904985 DOI: 10.1101/2023.10.19.563158
Abstract

The tumor suppressor LKB1 is a serine/threonine protein kinase that is frequently mutated in human lung adenocarcinoma (LUAD). LKB1 regulates a complex signaling network that is known to control cell polarity and metabolism; however, the pathways that mediate the tumor suppressive activity of LKB1 are incompletely defined. To identify mechanisms of LKB1- mediated growth suppression we developed a spheroid-based Cell Culture assay to study LKB1- dependent growth. Using this assay, along with genome-wide CRISPR screens and validation with orthogonal methods, we discovered that LKB1 suppresses growth, in part, by activating the PIKfyve lipid kinase, which promotes the internalization of wild-type EGFR. Our findings reveal a new mechanism of regulation of EGFR, which may have implications for the treatment of LKB1 -mutant LUAD.

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