PD-L1 promotes NSCLC Cell Proliferation

On 2 November, 2020, professor Zeyi Liu and Jian-an Huang from The First Affiffiffiliated Hospital of Soochow University published a paper on Cell Death and Difffferentiation. The paper titled KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway

In addition to the role of programmed cell death ligand 1 (PD-L1) in facilitating tumour cells escape from immune surveillance, it is considered as a crucial effffector in transducing intrinsic signals to promote tumour development. Our previous study has pointed out that PD-L1 promotes non-small cell lung cancer (NSCLC) cell proliferation, but the mechanism remains elusive. Here we fifirst demonstrated that PD-L1 expression levels were positively correlated with p-MerTK levels in patient samples and NSCLC cell lines. In addition, PD-L1 knockdown led to the reduced phosphorylation level of MerTK in vitro. We next showed that PD-L1 regulated NSCLC cell proliferation via Gas6/MerTK signaling pathway in vitro and in vivo. To investigate the underlying mechanism, we unexpectedly found that PD-L1 translocated into the nucleus of cancer cells which was facilitated through the binding of Karyopherin β1 (KPNB1). Nuclear PD-L1 (nPD-L1), coupled with transcription factor Sp1, regulated the synthesis of Gas6 mRNA and promoted Gas6 secretion to activate MerTK signaling pathway. Taken together, our results shed light on the novel role of nPD-L1 in NSCLC cell proliferation and reveal a new molecular mechanism underlying nPD-L1-mediated Gas6/MerTK signaling activation. All above fifindings provide the possible combinational implications for PD-L1 targeted immunotherapy in the clinic.

According to statistics, lung cancer is one of the fastest growing malignant tumors with high morbidity and mortality. Among the world cancer death causes, lung cancer ranks fifirst. Non-small cell lung cancer (NSCLC) accounts for about 85% of all diagnosed primary lung cancer, and small cell lung cancer (SCLC) accounts for about 20% to 25%. In recent years, with the deepening of lung cancer research, many tumor markers related to lung cancer have been found, which have important clinical value in the screening, diagnosis, effiffifficacy detection and prognosis of lung cancer.Cloud-Clone could provide multiple proteins, antibodies and ELISA kits of metabolic pathways related targets. At present, there are more than 100 publications using Cloud-Clone metabolic pathways related products.