GPR162 activates STING dependent DNA damage pathway as a novel tumor suppressor and radiation sensitizer

In the treatment of most malignancies,radiotherapy plays a significant role.However,the resistance of cancer cells to ionizing radiation(IR)is the main reason for the failure of radiotherapy,which causes tumor recurrence and metastasis.In this study,we confirmed that GPR162,an orphan receptor in the G-protein-coupled receptor family,acted as a novel radiotherapy sensitizer by interacting with the stimulator of interferon genes(STING),which targeted DNA damage responses,activated IRF3,accelerated the activation of type I interferon system,promoted the expression of chemokines including CXCL10 and CXCL4,and inhibited the occurrence and development of tumors.Interestingly,the activation of STING by overexpression of GPR162 was independent of the classical pathway of cGAS.STING inhibitors could resist the antitumor effect of overexpression of GPR162 in IR-induced mouse models.In addition,most solid tumors showed low expression of GPR162.And the higher expression of GPR162 indicated a better prognosis in patients with lung adenocarcinoma,liver cancer,breast cancer,etc.In summary,these results suggested that GPR162 may serve as a potential sensitizer of radiotherapy by promoting radiotherapy-induced STING-IFN production and increasing the expression of chemokines including CXCL10 and CXCL4 in DNA damage response,providing an alternative strategy for improving cancer radiotherapy.

Author Correction:GPR162 activates STING dependent DNA damage pathway as a novel tumor suppressor and radiation sensitizer

Since the publication of this article,we noticed a minor mistake in the article that needs to be corrected.We have checked the original data;the correct data are provided in this Corrigendum as follows.The key findings of the article are not affected by these corrections.

The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties

Posttranslational modifications(PTMs)of proteins,including chromatin modifiers,play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties.However,the roles of Lymphoid-specific helicase(LSH),a DNA methylation modifier,in modulating stem-like properties in cancer are still not clearly clarified.Therefore,exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH.Here,we demonstrate that LSH is capable to undergo PTMs,including methylation and phosphorylation.The arginine methyltransferase PRMT5 can methylate LSH at R309 residue,meanwhile,LSH could as well be phosphorylated by MAPK1 kinase at S503 residue.We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue,which eventually promoting stem-like properties in lung cancer.Whereas,phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties,indicating the critical roles of LSH PTMs in modulating stem-like properties.Thus,our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.