{Reference Type}: Journal Article
{Title}: Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase.
{Author}: Ferrarone JR;Thomas J;Unni AM;Zheng Y;Nagiec MJ;Gardner EE;Mashadova O;Li K;Koundouros N;Montalbano A;Mustafa M;Cantley LC;Blenis J;Sanjana NE;Varmus H;
{Journal}: Proc Natl Acad Sci U S A
{Volume}: 121
{Issue}: 21
{Year}: 2024 May 21
{Factor}: 12.779
{DOI}: 10.1073/pnas.2403685121
{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. We then performed genome-wide CRISPR screens in spheroidal culture and found that LKB1 suppresses growth, in part, by activating the PIKFYVE lipid kinase. Finally, we used chemical inhibitors and a pH-sensitive reporter to determine that LKB1 impairs growth by promoting the internalization of wild-type EGFR in a PIKFYVE-dependent manner.