On October 16, the international academic journal Cancer Research published online the latest research results of the research group Ji Hongbin of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss. This study not only revealed the new molecular mechanism of the tumor suppressor gene LKB1 in the progression and metastasis of lung cancer, but also found that the high expression of NEDD9 was positively correlated with the malignant progression and metastasis of lung cancer. This research will provide new potential therapeutic targets and prognostic-related biological markers for the clinical diagnosis and treatment of lung cancer.
Infiltration and metastasis is one of the most important biological characteristics of malignant tumors, and it is also the main reason that affects the efficacy of lung cancer and leads to patient death. Ji Hongbin's group has long been devoted to the molecular mechanism of lung cancer development and metastasis. Its previous research results show that about 30% of non-small cell lung cancers have functional deletion mutations of LKB1, while the study of mouse lung cancer models shows that the absence of LKB1 will Significantly promote lung cancer metastasis, suggesting that the tumor suppressor gene LKB1 plays an important role in the malignant progression and metastasis of lung cancer, but its molecular mechanism is poorly understood.
Under the guidance of Researcher Ji Hongbin, PhD students Feng Yan and Wang Ye, through a series of in vitro cell experiments and in vivo animal experiments, found that NEDD9 as an important downstream effector molecule, mediates the malignant progression and metastasis of lung cancer caused by LKB1 deletion. The study found that the high expression of NEDD9 promoted the development of KrasG12D primary lung tumors in mice; while the down-regulation of Nedd9 expression significantly inhibited the malignant progression of KrasG12D, Lkb1L / L primary mouse lung cancer; further mechanism research found LKB1 regulates the nucleoplasm translocation of the co-transcription factor CRTC1 through SIK2 to affect the transcriptional expression of NEDD9, thereby affecting the malignant progression of lung cancer.
In addition, the clinical correlation analysis results of 175 lung cancer samples showed that the high expression of NEDD9 in lung cancer was significantly related to clinical stage and lymph node metastasis, suggesting that NEDD9 is closely related to the malignant progression of lung cancer, and may be a potential new molecule to predict high metastasis of lung cancer. At the same time, NEDD9 may also become a molecular target for clinical treatment of malignant progression and metastasis of lung cancer.
This work was greatly assisted by Researcher Xiong Zhiqi of the Institute of Neurology and Researcher Zhai Qiwei of the Institute of Nutrition, and was supported by project funds from the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Shanghai Municipal Science and Technology Commission.
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