TY - JOUR
T1 - Why is autophagy important for melanoma? Molecular mechanisms and therapeutic implications
AU - Corazzari, Marco
AU - Fimia, Gian Maria
AU - Lovat, Penny
AU - Piacentini, Mauro
N1 - Funding Information:
This work was supported in part by grants from AIRC ( MFAG-11743 to M.C., IG2012 to G.M.F. and IG2010 to M.P. ), the Italian Ministry of University and Research ( PRIN 2012 and FIRB Accordi di Programma 2011 ) and the Italian Ministry of Health (Ricerca Finalizzata and Ricerca Corrente). This work was also founded by the British skin foundation, the Newcastle Healthcare Charity and the JW Patterson foundation (to P.E. Lovat).
PY - 2013/10
Y1 - 2013/10
N2 - As the principle lysosomal mediated mechanism for the degradation of aged or damaged organelles and proteins, autophagy (self-eating) is generally considered a pro-survival process activated by cells to sustain life in presence of adverse environmental conditions such as nutrient shortage and/or in presence of cytotoxic compounds [1]. Upon activation, cytoplasmic material is sequestered into double-membrane vesicles (autophagosomes) then targeted for degradation by fusion with lysosomes (autolysosomes); metabolic activity and cell survival are consequently sustained by recycling the degradation products. Basal autophagy occurs in almost all cell types, though at different degree, as a finely regulated quality control process to prevent cell damage, for the demolition of cellular structures during cell/tissue remodelling, and to ensure the maintenance of cellular homeostasis through recycling cellular components/molecules [2,3].Autophagy is stimulated in response to both physiological and pathological conditions such as starvation, hypoxia and low energy, pathogen infection and protein aggregates. Although it's clear that autophagy is also involved in cancer, its role, however, is complex since it can both suppress and promote tumorigenesis [4]. Consequently, it is generally accepted that while autophagy is used by advanced stage cancers to maintain tumour survival, loss of autophagy in earlier stages is associated with tumour development. Accordingly, it is now apparent that aberrant control of autophagy is among key hallmarks of cancer, with several studies now demonstrating this process is deregulated also in melanoma [5,6].
AB - As the principle lysosomal mediated mechanism for the degradation of aged or damaged organelles and proteins, autophagy (self-eating) is generally considered a pro-survival process activated by cells to sustain life in presence of adverse environmental conditions such as nutrient shortage and/or in presence of cytotoxic compounds [1]. Upon activation, cytoplasmic material is sequestered into double-membrane vesicles (autophagosomes) then targeted for degradation by fusion with lysosomes (autolysosomes); metabolic activity and cell survival are consequently sustained by recycling the degradation products. Basal autophagy occurs in almost all cell types, though at different degree, as a finely regulated quality control process to prevent cell damage, for the demolition of cellular structures during cell/tissue remodelling, and to ensure the maintenance of cellular homeostasis through recycling cellular components/molecules [2,3].Autophagy is stimulated in response to both physiological and pathological conditions such as starvation, hypoxia and low energy, pathogen infection and protein aggregates. Although it's clear that autophagy is also involved in cancer, its role, however, is complex since it can both suppress and promote tumorigenesis [4]. Consequently, it is generally accepted that while autophagy is used by advanced stage cancers to maintain tumour survival, loss of autophagy in earlier stages is associated with tumour development. Accordingly, it is now apparent that aberrant control of autophagy is among key hallmarks of cancer, with several studies now demonstrating this process is deregulated also in melanoma [5,6].
KW - Autophagy, Melanoma
KW - BRAF
KW - Chemoresistance
KW - Tumorigenesis
UR - http://www.scopus.com/inward/record.url?scp=84884812529&partnerID=8YFLogxK
U2 - 10.1016/j.semcancer.2013.07.001
DO - 10.1016/j.semcancer.2013.07.001
M3 - Review article
SN - 1044-579X
VL - 23
SP - 337
EP - 343
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
IS - 5
ER -