Adhesion-dependent regulation of Golgi organization and function in normal vs cancer cells

Abstract

Cancer cells are unique in overcoming the requirement for cell-matrix adhesion (anchorage dependence) to grow, proliferate and metastasize. Among the cellular pathways regulated by adhesion include its ability to control Golgi organization and function. In non- transformed cells, loss of adhesion causes dramatic disorganization of the Golgi accompanied by a change in cell surface glycosylation. Arf1 inhibitor-mediated disruption of the Golgi differentially affects the glycosylation signature of cells. If and how this adhesion-mediated regulation of Golgi is perturbed in cancers remains unclear. To address this, we screened multiple cancer cell lines for their Golgi organization when stable adherent and saw distinct changes. On loss of adhesion, some cancer cell lines interestingly maintained their intact Golgi organization, while others did not. This lead us to identify a pair of lung cancer cells, A549 and CaLu1, with distinct Golgi organizations. An extended screen of CCLE and other databases led us to shortlist differentially expressed genes (DEGs) between these lung cancer cell lines, which could potentially regulate their Golgi organization. Careful evaluation reveals the receptor tyrosine kinase AXL, detected to be localized in the Golgi, to mediate adhesion-independent Golgi organization in A549 cells. This work studies this regulation and evaluates how AXL-dependent Golgi organization could contribute to its oncogenic role in anchorage-independent lung adenocarcinoma cells.