Investigating Cooperation between KEAP1 and LKB1 Inactivation in Lung Adenocarcinoma
Technical Report,01 Aug 2017,31 Jul 2018
Dignity Health San Francisco United States
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Preliminary analysis in our laboratory reveals concurrent mutation of the LKB1 and KEAP1tumor suppressors correlate with poor overall survival in lung adenocarcinoma LA.Phenotypically, there is evidence to suggest that inactivation of KEAP1 may support adaptation to increased oxidative stress that results from LKB1 inactivation. We have found that inactivation of KEAP1 in the background of LKB1 inactivation results in increased growth and resistance to treatment. Further, we have evidence that cross-talk from the PERK kinase, may also further support adaptation to oxidative stress in combination with KEAP1inactivation in LKB1-deficient LA. These findings suggest that KEAP1LKB1 inactivation may represent a critical step in LA tumorigenesis and may have a role in therapeutic resistance. We are further exploring these findings using in vivo models.
- Medicine and Medical Research