Tumor Biology

, Volume 36, Issue 10, pp 7873–7879 | Cite as

LATS2 inhibits the activity of NF-κ B signaling by disrupting the interaction between TAK1 and IKKβ

Research Article

Abstract

NF-κB signaling plays very important role in the tumorigenesis of nonsmall cell lung cancer (NSCLC). However, the molecular mechanisms for the dysregulation of NF-κB signaling in NSCLC have not been fully understood. In the previous reports, we have showed that large tumor suppressor gene 2 (LATS2) inhibited NF-κB signaling in NSCLC cells, whereas the details for the mechanism remain unknown. Here, we reported that LATS2 is a suppressor of tumor necrosis factor (TNF-α)-induced NF-κB signaling by inhibiting the interaction between TAK1 and IKKβ. Overexpression of LATS2 largely blocked TNF-α-induced NF-κB activation and IκBα degradation, whereas knockdown of LATS2 showed the opposing results. Mechanistically, we identified that LATS2 interacted with IKKβ and blocked the interaction between IKKβ and TAK1. Our results indicate that LATS2 functions as a pivotal negative regulator in TNF-α-induced activation of NF-κB via disrupting the interaction of TAK1 with IKKβ.

Keywords

Nonsmall cell lung cancer NF-κB signaling LATS2 IKK complex TAK1 TNF-α 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81201840), the Natural Science Foundation of Shanghai (13ZR1461300), the Health Bureau Foundation of Shanghai (20124Y152), and Chenxing Young Scholarship of Shanghai Jiaotong University.

Conflict of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Thoracic Surgery, Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of Cardiothoracic Surgery, Changhai HospitalSecond Military Medical UniversityShanghaiChina

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