Secretome analysis of human A549 Lung cancer cells harboring LKB1 mutations.

ABSTRACT: STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation. Elucidating the contribution of somatic mutations to cancer is essential for personalized medicine. STK11 (LKB1) tumor suppressor appears to be inactivated in human cancer, however, somatic missense mutations also occur. Despite of our increased knowledge about LKB1 function, the role/s of these alterations in cancer are mostly unknown. Here, we investigated the contribution of four missense LKB1 somatic mutations in tumor biology. Three, out of the four mutants, lost their tumor suppressor capabilities and showed a deficient kinase activity. The remaining mutant conserved the enzymatic activity, but conferred an increased cell motility. Mechanistically, LKB1 mutants promoted the differential gene expression regulation of vesicle trafficking regulating molecules, adhesion molecules and cytokines, that correlated with the identified protein networks associated to the comparative secretome analysis. Notably, three mutant isoforms promoted tumor growth, and one of them induced inflammation and hemorrhagic tumors that correlated with the deregulated levels of cytokines. Altogether, our findings uncover oncogenic roles of LKB1 somatic mutations helping to understand their contribution to cancer.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell, Cell Culture

DISEASE(S): Lung Cancer

SUBMITTER: Francesc Canals  

LAB HEAD: Juan A. Recio

PROVIDER: PXD018041 | Pride | 2021-09-09

REPOSITORIES: Pride