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Lysosomal Function ...
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Eriksson, IdaLinköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
(författare)
Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Melanoma
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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ELSEVIER SCIENCE INC,2023
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-198080
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-198080URI
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https://doi.org/10.1016/j.jid.2023.01.036DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies|Swedish Cancer Society [CAN-190396]; Hudfonden (Welander-Finsen Foundation); Forskningsradet i Sydostra Sverige; Ostgotaregionens Cancer Foundation; County Council of Ostergotland; Borghamns Rotary Club
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Lysosomes are central in cell homeostasis and participate in macromolecular degradation, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. In cancer, alterations in lysosomal function and spatial distribution may facilitate disease progression. In this study, we show enhanced lysosomal activity in malignant melanoma cells compared with that in normal human melanocytes. Most lysosomes show perinuclear location in melanocytes, while they are more dispersed in melanoma, with retained proteolytic activity and low pH also in the peripheral population. Rab7a expression is lower in melanoma cells than in melanocytes, and by increasing Rab7a, lysosomes are relocated to the perinuclear region in melanoma. Exposure to the lysosome-destabilizing drug L-leucyl-L-leucine methyl ester causes higher damage in the perinuclear subset of lysosomes in melanomas, whereas differences in subpopulation susceptibility cannot be found in melanocytes. Interestingly, melanoma cells recruit the endosomal sorting complex required for transport-III core protein CHMP4B, involved in lysosomal membrane repair, rather than initiate lysophagy. However, when the perinuclear lysosomal position is promoted by Rab7a overexpression or kinesore treatment, lysophagy is increased. In addition, Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Vainikka, LindaLinköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten(Swepub:liu)linva19
(författare)
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Wäster, PetraLinköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten(Swepub:liu)petla10
(författare)
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Öllinger, KarinLinköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten(Swepub:liu)karol56
(författare)
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Linköpings universitetAvdelningen för cellbiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Investigative Dermatology: ELSEVIER SCIENCE INC143:9, s. 1769-+0022-202X1523-1747
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