TIMP-1 Dependent Modulation of Metabolic Profiles Impacts Chemoresistance in NSCLC.

ABSTRACT: The development of chemoresistance remains a significant barrier to treating NSCLC. Alteration of cancer cell metabolism is an important mechanism for chemoresistance. This study explored the role of aberrant metabolism in TIMP-1-mediated chemoresistance. Bioinformatics analysis identified an association of high TIMP-1 with altered energy metabolism. We have defined the role of depolarized mitochondria through a reduction in lactate secretion, higher ROS levels in TIMP-1 KD cells and reduced GSH levels. TIMP-1 modulates the metabolic profile via acetylation of mitochondrial STAT3 and its interaction with CD44. Intriguingly, monomers of acetylated STAT3 were critical for altered metabolism, whereas STAT3 dimers abrogated this function. Further, the mitochondrial metabolic profile was also a

SUBMITTER: Xiao W 

PROVIDER: S-EPMC9562647 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature