Our study delineates a novel pharmacological strategy to promote the degradation of HK2 in cancer cells. Autophagy is a catabolic mechanism responsible for the degradation of cellular components via the lysosomal pathway and plays a pivotal role in maintaining protein homeostasis and protecting cells in stress conditions such as nutrient shortage or oxidative stress Citation 1. We reveal a new mechanism by which excessive activation of CMA may be exploited pharmacologically to eliminate cancer cells by inhibiting both FLT3 and autophagy. Macroautophagy is the most studied form of autophagy. Esophageal cancer is a malignant tumor type prevalent in developing countries, with a poor 5-year survival rate of about 30.4. Chaperone-mediated autophagy is a form of selective autophagy which relies on the recognition of chaperons via targeted motif in the degrading proteins and lysosomal chaperons (45, 46). Lysosomal membrane associated protein 2a. Importantly, our proteome analysis revealed that HK2 is a CMA substrate and that its degradation by CMA is regulated by glucose availability. Keywords: Autophagy, Chaperone-mediated autophagy, Chronic obstructive pulmonary disease, Lung cancer Background Autophagy is a highly conserved mechanism of delivering cytoplasmic components for lysosomal degradation to maintain the homeostatic balance between the synthesis, degradation, and recycling of cellular proteins and organelles 1. Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Our data demonstrate that FLT3 is an important sensor of cellular nutritional state and elucidate the role and molecular mechanism of CMA in metabolic regulation and mediating cancer cell death. Autophagy is a highly conserved mechanism of delivering cytoplasmic components for lysosomal degradation. CMA is a form of autophagy in which substrates are directly targeted to the lysosome for degradation upon binding with the cytosolic chaperone HSC70 and further interaction with the cytosolic tail of the lysosome-associated membrane protein. Here we show that metabolic stress triggered by perturbation of receptor tyrosine kinase FLT3 in non–acute myeloid leukemia cells sensitizes cancer cells to autophagy inhibition and leads to excessive activation of chaperone-mediated autophagy (CMA). Autophagy in cancer: friend or foe Silvia Vega-Rubn-de-Celis, in Autophagy in Health and Disease (Second Edition), 2022. Abstract Hexokinase II (HK2), a key enzyme involved in glucose metabolism, is regulated by growth factor signaling and is required for initiation and maintenance of tumors.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |