Loxl3 promotes melanoma progression and dissemination influencing cell plasticity and survival
Entity
UAM. Departamento de BioquímicaPublisher
MDPIDate
2022-02-25Citation
10.3390/cancers14051200
Cancers 14.5 (2022): 1200
ISSN
2072-6694 (online)DOI
10.3390/cancers14051200Editor's Version
https://doi.org/10.3390/cancers14051200Subjects
LOXL3; melanoma; melanoma metastasis; genetic mouse model; EMT; cellular plasticity; SNAIL1; PRRX1; phenotype switching; MedicinaRights
© 2022 by the authorsAbstract
Malignant melanoma is a highly aggressive tumor causing most skin cancer-related deaths.
Understanding the fundamental mechanisms responsible for melanoma progression and therapeutic
evasion is still an unmet need for melanoma patients. Progression of skin melanoma and its dissemination to local or distant organs relies on phenotypic plasticity of melanoma cells, orchestrated
by EMT-TFs and microphthalmia-associated TF (MITF). Recently, melanoma phenotypic switching
has been proposed to uphold context-dependent intermediate cell states benefitting malignancy.
LOXL3 (lysyl oxidase-like 3) promotes EMT and has a key role in human melanoma cell survival
and maintenance of genomic integrity. To further understand the role of Loxl3 in melanoma, we
generated a conditional Loxl3-knockout (KO) melanoma mouse model in the context of BrafV600Eactivating mutation and Pten loss. Melanocyte-Loxl3 deletion increased melanoma latency, decreased
tumor growth, and reduced lymph node metastatic dissemination. Complementary in vitro and
in vivo studies in mouse melanoma cells confirmed Loxl3’s contribution to melanoma progression
and metastasis, in part by modulating phenotypic switching through Snail1 and Prrx1 EMT-TFs.
Importantly, a novel LOXL3-SNAIL1-PRRX1 axis was identified in human melanoma, plausibly
relevant to melanoma cellular plasticity. These data reinforced the value of LOXL3 as a therapeutic
target in melanoma
Files in this item
Google Scholar:Vázquez Naharro, Alberto
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Bustos Tauler, José
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Floristán, Alfredo
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Yuste, Lourdes
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Oltra, Sara S.
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Vinyals, Antònia
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Moreno Bueno, Gema
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Fabra, Àngels
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Portillo Pérez, Francisco
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Cano, Amparo
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Santamaría, Patricia G.
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