Table 1.
Description of the CMA activities and regulations involved in glioma features and responsiveness to treatments.
| Key Player | Relation with Glioma | References | |
|---|---|---|---|
| CMA regulation in glioma | Dynein | It is involved in autophagosome trafficking and LAMP-2A localization. It has been targeted with therapeutic purposes to block CMA. | [71] |
| TFEB | Highly expressed in glioblastoma cells responsive to TMZ. | [54] | |
| LAMP-2A | LAMP-2A high level correlates with a worse prognosis. | [69] | |
| HSC70 | Commonly expressed in glioma, lysosomal HSC70 is related to glioma grade. | [8,75] | |
| PHLPP1 | PHLPP1 down-regulation has been found in several tumors including glioma. | [8,73,74] | |
| CMA targets in glioma | Chk-1 | TMZ treatment induces Chk1 phosphorylation and consequent degradation through CMA. | [67] |
| HIF-1α | HIF-1α reduction in glioma cells has been related to TMZ treatment efficacy. | [8,9,22,54] | |
| Other CMA target | Several tumor suppressors and oncogenes involved in tumorigenesis are CMA targets (such as mutant p53, BBC3/PUMA, HK2, etc) but still need further investigation in glioma. | [10,15,50,51] | |
| CMA and glioma treatments | TMZ | Autophagy inducer: ROS-mediated induction of CMA activity in relation to responsiveness to the treatment. | [8,65,66] |
| ROS | CMA inducer: oxidative stress helps in overcoming TMZ resistance. | [8] | |
| RA | CMA inducer: LAMP2A stabilization; it supports the cytotoxic effect of TMZ treatment. | [68] | |
| Digoxin | CMA inducer: reduces glioma growth and increases tumour sensitivity to anticancer treatments. | [54] | |
| Lovastatine | Autophagy inhibitor: reduces LAMP-2A and dynein levels. Used with TMZ to enhance its efficacy. | [71,72] | |
| Bafilomycin | Autophagy a-specific inhibitor: reduces cancer stem cell viability and increases HIF-1α level. | [54,82] | |
| Chloroquine | Autophagy a-specific inhibitor: adjuvant for RT, its role is still controversial in different models and conditions. | [54,83] | |
| CMA activity and immune response in glioma | T regs | PHLPP1 induces negative modulation of Treg and the consequent increase of specific adaptive immune response against glioma. | [39,78] |
| Machropages | PHLPP1 blocks STAT-1 activity, inhibiting innate immune response. | [11,79,81] | |
| Perycites | CMA activation induces anti-inflammatory microenvironment and glioma immune-tolerance. | [3] |