Maayan Baron

Abstract Desmosomes are transmembrane protein complexes that contribute to cell-cell adhesion in epithelia and other tissues. Here, we report the discovery of frequent genetic alterations in the desmosome in human cancers, with the strongest signal seen in cutaneous melanoma where desmosomes are mutated in over 70% of cases. In primary but not metastatic melanoma biopsies, the burden of coding mutations on desmosome genes associates with a strong reduction in desmosome gene expression.

Highlights • Melanomas exhibit 3 cell states: neural-crest, mature melanocyte, and stress-like • The stress-like cancer cell state is conserved across tumor types and species • Stress-like cancer cells are pro-tumorigenic and efficient at seeding new tumors • Stress-like cancer cells hold drug-resistant properties induced by heat shock Summary Transcriptional profiling of tumors has revealed a stress-like state among the cancer cells with the concerted expression of genes such as fos, jun,...

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