An inverse relationship between autophagy and CAV1 has also been observed in models of nontransformed cells. For instance, metabolomic profiling of endothelial cell lysates following transfection with si-CAV1 or si-control resulted in marked increases in dipeptide levels for the CAV1 knockdown cells, which was attributed to an increase in autophagy [129]. To corroborate these results, the authors evaluated the processing of LC3 I to LC3 II by western blotting and showed that siRNA-mediated CAV1 knockdown led to an increase in the presence of the autophagy marker LC3-II. Also, treatment with the lysosomal inhibitor bafilomycin A1 markedly increased LC3-II levels, indicating that reduced CAV1 expression leads to an increase in autophagy flux [129]. Recently, CAV1 was also shown to regulate autophagy in cigarette smoking-induced injury of lung epithelium [130]. Specifically, CAV1 depletion increased basal and starvation-induced levels of ATG12-ATG5 and autophagy. Biochemical analysis revealed that CAV1 interacted with ATG5, ATG12, and the active ATG12-ATG5 complex to suppress autophagy in lung epithelial cells, thereby providing new insights as to how CAV1 modulates autophagy in this model [130]. However, details of the molecular mechanisms by which CAV1 regulates autophagy in cancer cells remain to be determined. A rather speculative idea is that the dual role of CAV1 in cancer may be linked to its participation in the control of autophagy. However, further experimentation is required to corroborate this intriguing hypothesis.
Cell And Molecular Biology By Gerald Karp Pdf 831
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