PMID- 33672324
OWN - NLM
STAT- MEDLINE
DCOM- 20210601
LR  - 20240331
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 23
TI  - The Multifaceted Role of CMA in Glioma: Enemy or Ally?
LID - 10.3390/ijms22042217 [doi]
LID - 2217
AB  - Chaperone-mediated autophagy (CMA) is a catabolic pathway fundamental for cell 
      homeostasis, by which specific damaged or non-essential proteins are degraded. 
      CMA activity has three main levels of regulation. The first regulatory level is 
      based on the targetability of specific proteins possessing a KFERQ-like domain, 
      which can be recognized by specific chaperones and delivered to the lysosomes. 
      Target protein unfolding and translocation into the lysosomal lumen constitutes 
      the second level of CMA regulation and is based on the modulation of Lamp2A 
      multimerization. Finally, the activity of some accessory proteins represents the 
      third regulatory level of CMA activity. CMA's role in oncology has not been fully 
      clarified covering both pro-survival and pro-death roles in different contexts. 
      Taking all this into account, it is possible to comprehend the actual complexity 
      of both CMA regulation and the cellular consequences of its activity allowing it 
      to be elected as a modulatory and not only catabolic machinery. In this review, 
      the role covered by CMA in oncology is discussed with a focus on its relevance in 
      glioma. Molecular correlates of CMA importance in glioma responsiveness to 
      treatment are described to identify new early efficacy biomarkers and new 
      therapeutic targets to overcome resistance.
FAU - Lo Dico, Alessia
AU  - Lo Dico A
AUID- ORCID: 0000-0002-8627-5050
AD  - Department of Pathophysiology and Transplantation, University of Milan, Via 
      F.Cervi 93, Segrate, 20090 Milan, Italy.
FAU - Martelli, Cristina
AU  - Martelli C
AUID- ORCID: 0000-0003-0023-9110
AD  - Department of Pathophysiology and Transplantation, University of Milan, Via 
      F.Cervi 93, Segrate, 20090 Milan, Italy.
FAU - Diceglie, Cecilia
AU  - Diceglie C
AUID- ORCID: 0000-0003-1749-1080
AD  - Department of Pathophysiology and Transplantation, University of Milan, Via 
      F.Cervi 93, Segrate, 20090 Milan, Italy.
FAU - Ottobrini, Luisa
AU  - Ottobrini L
AUID- ORCID: 0000-0002-5002-6845
AD  - Department of Pathophysiology and Transplantation, University of Milan, Via 
      F.Cervi 93, Segrate, 20090 Milan, Italy.
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council 
      (IBFM-CNR), Via F.Cervi 93, Segrate, 20090 Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210223
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - EC 3.1.3.16 (PHLPP1 protein, human)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Antineoplastic Agents, Alkylating/pharmacology
MH  - *Chaperone-Mediated Autophagy/drug effects/physiology
MH  - Glioma/*drug therapy/metabolism/*pathology
MH  - Humans
MH  - Nuclear Proteins/metabolism
MH  - Phosphoprotein Phosphatases/metabolism
MH  - Proteins/metabolism
MH  - Temozolomide/pharmacology
PMC - PMC7926390
OTO - NOTNLM
OT  - Hypoxia Inducible Factor-1alpha (HIF-1alpha)
OT  - PHLPP1
OT  - Temozolomide (TMZ)
OT  - autophagy
OT  - chaperone proteins
OT  - oxidative stress
OT  - therapeutic target
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/07 06:00
MHDA- 2021/06/02 06:00
PMCR- 2021/02/23
CRDT- 2021/03/06 01:13
PHST- 2021/01/30 00:00 [received]
PHST- 2021/02/18 00:00 [revised]
PHST- 2021/02/20 00:00 [accepted]
PHST- 2021/03/06 01:13 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/06/02 06:00 [medline]
PHST- 2021/02/23 00:00 [pmc-release]
AID - ijms22042217 [pii]
AID - ijms-22-02217 [pii]
AID - 10.3390/ijms22042217 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 23;22(4):2217. doi: 10.3390/ijms22042217.