CHST11 Promotes Lung Cancer Metastasis through Changing Intracellular Iron Metabolism

Abstract

Non‐small‐cell lung cancer (NSCLC) is one of the most lethal cancers, for it often develops metastasis after therapy. Cancer metastasis usually begins from epithelial‐to‐mesenchymal transition (EMT), and metabolic disorder is a key mediator of lung cancer EMT. The linkage between metabolic disorder and NSCLC EMT is still unclear. Here, we compared gene expression signatures from both TGFb induction EMT model of NSCLC cells and the EMT score from clinical NSCLC patients' cohort. We found several chondroitin sulfate (CS) biosynthesis genes were highly correlated to NSCLC EMT status. CHST11, the key enzyme of this pathway, was selected for further functional studies. Enforced CHST11 expression promoted NSCLC cells migration, invasion and increasing M‐type markers, such as Slug, N‐cadherin and Vimentin expression and vise versa. Deplete the final product of CS biosynthesis by chondroitinase ABC or enzyme‐dead CHST11 could abolish the NSCLC EMT ability from TGFb and CHST11, respectively. Moreover, we found the CHST11 expression changing the iron metabolic status in NSCLC cells and promoting the NSCLC EMT.In the end, immunohistochemistry showed that CHST11 was a poor prognostic marker of overall survival and disease‐free survival in clinical NSCLC patients. In conclusion, our findings implicated that 1) The chondroitin sulfate biosynthesis pathways is crucial for NSCLC EMT; 2) A novel CHST11‐CP‐Fe3+ pathway is involved in NSCLC EMT. 3) CHST11 is a poor prognostic marker in NSCLC patients. These results might help us to understand the role of aberrant cancer metabolism in NSCLC EMT.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.