TFEB mediated autophagy upregulate to inhibit apoptosis in
endometriosis
Autophagy and apoptosis are the main factors determining cell fate.
Apoptosis is a kind of cell death characterized by cell atrophy,
chromatin condensation and other morphological changes. Autophagy, which
means ”self-feeding” is an important degradation pathway to eliminate
protein aggregation and damaged organelles in cells.(74) More and more
evidence show that apoptosis and autophagy have antagonistic effects.
Autophagy helps human cancer cells survive through apoptotic resistance,
and inhibition of autophagy leads to caspase-dependent apoptotic cell
death.(75) In tumor microenvironment, inhibition of autophagy disrupts
cell metabolism, causes genomic instability, interferes with
differentiation, and destroys anti-cancer immune surveillance. During
tumor development, cancer cells are exposed to different types of
stress, including nutritional deficiency, metabolic stress and hypoxia,
especially in the central region of the tumor. Autophagy can be
reinstated which can increase the resistance of cancer cells to
chemotherapy or radiotherapy.(76) The cytoprotective effect of autophagy
can maintain the survival ability of tumor cells and prevent the
apoptosis of cancer cells.(77) In nucleus pulposus cells, TFEB
overexpression enhanced autophagy flux and lysosome function, which
further protected nucleus pulposus cells from apoptosis and senescence
induced by TBHP (ROS donor induced oxidative stress).(78) The same
mechanism may exist in endometriosis. In early stage of endometriosis,
inhibition of autophagy disrupts cell metabolism, interferes with
differentiation, and evades immune surveillance. As the disease
progresses, excessive ROS activates TFEB in different ways, and
overexpression of TFEB promotes the expression of autophagy-related
proteins, increases the autophagy flux and lysosome synthesis,thus
maintaining cell growth and inhibiting apoptosis, leading to the
worsening of endometriosis. It was reported that the expression of Bcl-2
was increased in ectopic endometriosis in ovarian endometriosis
patients. Bcl-2 is an important anti-apoptotic regulator, and its
increase is associated with impaired spontaneous apoptosis, indicating
that apoptosis is decreased in endometrioma.(79)