Melanoma Stem Cell Maintenance and Chemo-Resistance Are Mediated by CD133 Signal to PI3K-Dependent Pathways

The functional analysis of CD133+ and CD133 cells in vitro and in vivo revealed that melanoma progression and treatment resistance are the consequences of CD133 signal to PI3K pathway.
[Oncogene]
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Single-Cell Sequencing of Genomic DNA Resolves Sub-Clonal Heterogeneity in a Melanoma Cell Line

Researchers performed shallow single-cell sequencing of genomic DNA across 1475 cells from a melanoma cell-line, COLO829 (a benchmark for evaluating somatic alterations) to resolve overall complexity and clonality.
[Communications Biology]
Velazquez-Villarreal, E. I., Maheshwari, S., Sorenson, J., Fiddes, I. T., Kumar, V., Yin, Y., Webb, M. G., Catalanotti, C., Grigorova, M., Edwards, P. A., Carpten, J. D., & Craig, D. W. (2020). Single-cell sequencing of genomic DNA resolves sub-clonal heterogeneity in a melanoma cell line. Communications Biology, 3(1), 1–8. https://doi.org/10.1038/s42003-020-1044-8 Cite
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The Hippo Pathway Oncoprotein YAP Promotes Melanoma Cell Invasion and Spontaneous Metastasis

To analyze the Hippo pathway in cutaneous melanoma, researchers generated a transcriptional signature of melanoma cells that overexpressed YAP, the key downstream Hippo pathway oncoprotein.
[Oncogene]
Zhang, X., Yang, L., Szeto, P., Abali, G. K., Zhang, Y., Kulkarni, A., Amarasinghe, K., Li, J., Vergara, I. A., Molania, R., Papenfuss, A. T., McLean, C., Shackleton, M., & Harvey, K. F. (2020). The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-1362-9 Cite
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TERT Promoter Mutation Determines Apoptotic and Therapeutic Responses of BRAF-Mutant Cancers to BRAF and MEK Inhibitors: Achilles Heel

Using thyroid cancer, melanoma, and colon cancer cell models, the authors showed that dabrafenib and trametinib induced robust apoptosis of cancer cells harboring both BRAF V600E and TERT promoter mutations but had little proapoptotic effect in cells harboring only BRAF V600E.
[Proceedings of the National Academy of Sciences of the United States of America]
Tan, J., Liu, R., Zhu, G., Umbricht, C. B., & Xing, M. (2020). TERT promoter mutation determines apoptotic and therapeutic responses of BRAF-mutant cancers to BRAF and MEK inhibitors: Achilles Heel. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2004707117 Cite
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miR-410-3p Is Induced by Vemurafenib via ER Stress and Contributes to Resistance to BRAF Inhibitor in Melanoma

Scientists showed a novel mechanism of melanoma resistance. miR-410-3p was induced by vemurafenib in melanoma cells via ER stress. It drove switching to the invasive phenotype that led to the response and resistance to BRAF inhibition.
[PLoS One]
Grzywa, T. M., Klicka, K., Paskal, W., Dudkiewicz, J., Wejman, J., Pyzlak, M., & Włodarski, P. K. (2020). miR-410-3p is induced by vemurafenib via ER stress and contributes to resistance to BRAF inhibitor in melanoma. PLOS ONE, 15(6), e0234707. https://doi.org/10.1371/journal.pone.0234707 Cite
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Polyphenolic Composition and Anti-Melanoma Activity of White Forsythia (Abeliophyllum distichum Nakai) Organ Extracts

The authors investigated the potential anticancer effect of Abeliophyllum distichum organ extracts against human melanoma SK-MEL-2 cells. The methanol extract of A. distichum leaves exhibited dose- and time-dependent cytotoxicities against SK-MEL-2 cells but not against HDFa human dermal fibroblasts.
[Plants ]
Yoo, T.-K., Kim, J.-S., & Hyun, T. K. (2020). Polyphenolic Composition and Anti-Melanoma Activity of White Forsythia (Abeliophyllum distichum Nakai) Organ Extracts. Plants, 9(6), 757. https://doi.org/10.3390/plants9060757 Cite
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Multi-Omic Analysis Reveals Significantly Mutated Genes and DDX3X as a Sex-Specific Tumor Suppressor in Cutaneous Melanoma

Researchers performed a mutation significance study of over 1,000 melanoma exomes, combined with a multi-omic analysis of 470 cases from The Cancer Genome Atlas.
[Nature Cancer]
Alkallas, R., Lajoie, M., Moldoveanu, D., Hoang, K. V., Lefrançois, P., Lingrand, M., Ahanfeshar-Adams, M., Watters, K., Spatz, A., Zippin, J. H., Najafabadi, H. S., & Watson, I. R. (2020). Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma. Nature Cancer, 1(6), 635–652. https://doi.org/10.1038/s43018-020-0077-8 Cite
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Disseminated Melanoma Cells Transdifferentiate into Endothelial Cells in Intravascular Niches at Metastatic Sites

Researchers combined lineage tracing in a spontaneous metastatic mouse model of melanoma, advanced imaging, and single-cell RNA sequencing approaches to search for pathophysiologically relevant melanoma cellular states.
[Cell Reports]
Li, X., Karras, P., Torres, R., Rambow, F., Oord, J. van den, Marine, J.-C., & Kos, L. (2020). Disseminated Melanoma Cells Transdifferentiate into Endothelial Cells in Intravascular Niches at Metastatic Sites. Cell Reports, 31(11). https://doi.org/10.1016/j.celrep.2020.107765 Cite
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Intratumoral Immune Activation with TLR4 Agonist Synergizes with Effector T Cells to Eradicate Established Murine Tumors

Scientists combined intratumoral administration of the synthetic toll-like receptor 4 agonist glucopyranosyl lipid A with either active vaccination or adoptive transfer of tumor-specific CD8 T cells to mice bearing established melanomas.
[Npj Vaccines]
Intratumoral immune activation with TLR4 agonist synergizes with effector T cells to eradicate established murine tumors | npj Vaccines. (n.d.). Retrieved June 16, 2020, from https://www.nature.com/articles/s41541-020-0201-x Cite
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Massively Parallel Reporter Assays of Melanoma Risk Variants Identify MX2 as a Gene Promoting Melanoma

Researchers showed that melanocyte-specific expression of human MX2 in a zebrafish model demonstrated accelerated melanoma formation in a BRAFV600E background.
[Nature Communications]
Choi, J., Zhang, T., Vu, A., Ablain, J., Makowski, M. M., Colli, L. M., Xu, M., Hennessey, R. C., Yin, J., Rothschild, H., Gräwe, C., Kovacs, M. A., Funderburk, K. M., Brossard, M., Taylor, J., Pasaniuc, B., Chari, R., Chanock, S. J., Hoggart, C. J., … Brown, K. M. (2020). Massively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma. Nature Communications, 11(1), 2718. https://doi.org/10.1038/s41467-020-16590-1 Cite
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Failed Apoptosis Enhances Melanoma Cancer Cell Aggressiveness

Using a cancer cell model to trigger non-lethal caspase activation, the authors found that melanoma cancer cells undergoing failed apoptosis have a particular transcriptomic signature associated with focal adhesions, transendothelial migration, and modifications of the actin cytoskeleton.
[Cell Reports]
Berthenet, K., Ferrer, C. C., Fanfone, D., Popgeorgiev, N., Neves, D., Bertolino, P., Gibert, B., Hernandez-Vargas, H., & Ichim, G. (2020). Failed Apoptosis Enhances Melanoma Cancer Cell Aggressiveness. Cell Reports, 31(10). https://doi.org/10.1016/j.celrep.2020.107731 Cite
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