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The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss

Yan Feng1, Ye Wang, Zuoyun Wang

  • 1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Cancer Research
|October 18, 2012
PubMed

Insights

Loss of the LKB1 tumor suppressor gene in lung cancer promotes tumor growth and spread. The oncogene NEDD9 acts as a key mediator, driving progression when LKB1 is lost.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Somatic mutations in the LKB1 tumor suppressor gene are common in lung cancer, driving tumor progression and metastasis.
  • The molecular mechanisms linking LKB1 loss to lung cancer progression are not fully understood.

Purpose of the Study:

  • To elucidate the downstream mediators of LKB1 loss in lung cancer progression.
  • To investigate the role of the oncogene NEDD9 in LKB1-deficient lung cancer.

Main Methods:

  • Utilized de novo mouse models of lung cancer.
  • Employed RNA interference (RNAi) to silence Nedd9 expression.
  • Assessed the effects of ectopic NEDD9 and CRTC1 expression.
  • Analyzed clinical lung cancer specimens for NEDD9 expression levels.

Main Results:

  • Silencing Nedd9 inhibited lung tumor progression in mouse models.
  • Ectopic NEDD9 expression accelerated lung tumor progression.
  • LKB1 loss leads to increased NEDD9 transcription via CRTC1 nuclear export.
  • Elevated NEDD9 expression in clinical samples correlated with advanced malignancy and metastasis.

Conclusions:

  • NEDD9 is a critical downstream mediator of lung cancer progression following LKB1 loss.
  • The LKB1-CRTC1-NEDD9 axis represents a novel mechanism driving lung cancer malignancy.
  • Targeting NEDD9 may offer a therapeutic strategy for LKB1-deficient lung cancers.

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