PDLIM2 in Lung Adenocarcinoma Metastasis

Abstract

Human and mouse studies have established the unique PDZ-LIM domain-containing protein PDLIM2 as a common tumor suppressor that is especially vital for suppressing the tumorigenesis and therapeutic resistance of lung cancer, the leading cause of cancer-related deaths among both men and women. However, the role of PDLIM2 in tumor metastasis, the predominant cause of cancer morbidity and mortality, is yet to be determined. Here, we report that PDLIM2 repression was positively associated with the metastasis of human lung adenocarcinoma, the major type of non-small cell lung cancer that accounts for more than 40% of all cases of human lung cancer. Interestingly, PDLIM2 repression was also correlated with oncogenic KRAS and/or TP53 mutations, two common drivers of human lung adenocarcinoma that often co-occur. In mice, in comparison to concurrently inducing mutant KRAS expression and TP53 deletion, additional co-ablation of PDLIM2 significantly increased the number and size of lung adenocarcinomas in the lung, and more importantly, the distant metastasis of lung tumor cells. The increased metastasis was accompanied by decreased anti-tumor immunity and increased pro-tumor inflammation. These data demonstrate the role of PDLIM2 in suppressing lung adenocarcinoma metastasis, thereby improving our understanding of this crucial tumor suppressor and lung cancer. They also provide a useful model for studying metastasis and testing new lung cancer treatments in vivo.