New Study Reveals Mechanism of Lung Cancer Progression Evoked by LKB1 Loss

Somatic mutation of the tumor suppressor gene LKB1 is frequently observed in ~30% of non-small cell lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown. Now researchers from Chinese Academy of Sciences reveal that the oncogene NEDD9 is an important downstream mediator of lung cancer progression evoked by LKB1 loss.

 

NEDD9 is a non-catalytic scaffold protein, and has been implicated in the metastatic behavior of several types of solid tumors. However, the interactive regulation between LKB1 and NEDD9, and the potential functional contribution of such a network to lung cancer progression and metastasis have not been explored yet. In this study, Dr. Ji Hongbin’s group from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences provided strong evidences for NEDD9 as an important downstream mediator in LKB1-deficient lung cancer progression. In de novo mouse models, RNAi-mediated silencing of Nedd9 inhibited lung tumor progression, whereas ectopic NEDD9 expression accelerated this process.

 

Also, it uncovered a novel mechanism of LKB1 in contribution to lung cancer progression through CRTC1-NEDD9 axis. LKB1 negatively regulated NEDD9 transcription by promoting cytosolic translocation of CRTC1 from the nucleus. Moreover, elevated expression of NEDD9 was strongly associated with poor differentiation, advanced clinical stage, as well as lymph node metastasis of human lung cancer specimens. This study provides novel functional evidences and mechanistic insights into lung cancer progression and metastasis evoked by LKB1 loss and define a potential biomarker for lung cancer prognosis in clinic.

 

This work entitled ”The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss” was published online in Cancer Research on October 16^th, 2012. This project was supported by Ministry of Science and Technology of China, National Natural Science Foundation of China, and Chinese Academy of Sciences.

 

CONTACT:

JI Hongbin

Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China

Email: hbji@sibs.ac.cn, Tel: +86-21-54921108