Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Published: January 2020
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Article Abstract
Cutaneous malignant melanoma is an aggressive cancer of melanocytes with a strong propensity to metastasize. We posit that melanoma cells acquire metastatic capability by adopting an embryonic-like phenotype, and that a lineage approach would uncover metastatic melanoma biology. Using a genetically engineered mouse model to generate a rich melanoblast transcriptome dataset, we identify melanoblast-specific genes whose expression contribute to metastatic competence and derive a 43-gene signature that predicts patient survival. We identify a melanoblast gene, KDELR3, whose loss impairs experimental metastasis. In contrast, KDELR1 deficiency enhances metastasis, providing the first example of different disease etiologies within the KDELR-family of retrograde transporters. We show that KDELR3 regulates the metastasis suppressor, KAI1, and report an interaction with the E3 ubiquitin-protein ligase gp78, a regulator of KAI1 degradation. Our work demonstrates that the melanoblast transcriptome can be mined to uncover targetable pathways for melanoma therapy.
Dermal hyperpigmentation stands out among the various skin pigmentation phenotypes in chickens, where most other pigmentation variants affect feather color and patterning predominantly. Despite numerous black chicken breeds worldwide, only a select few exhibit comprehensive black pigmentation, which encompasses the skin, meat, flesh, and bones. The process of skin melanin pigmentation is intricate and develops successively.
Cellular quiescence is a reversible and tightly regulated stem cell function essential for healthy aging. However, the elements that control quiescence during aging remain poorly defined. Using melanocyte stem cells (McSCs), we find that stem cell quiescence is neither passive nor static.
The precise role played by the tumor suppressor gene in melanocyte biology and during the transformation into melanoma is not completely understood. In particular, understanding the interaction during melanocyte development between and key signaling pathways, which are known to be reactivated in advanced melanoma, is still under investigation. Here, we used RNAseq datasets from either situation to better understand the transcriptomic regulation mediated by an partial loss of function.
Background: Pharmacologic inhibition of bromodomain and extra-terminal (BET) proteins is currently being explored as a new therapeutic approach in cancer. Some studies have also implicated BET proteins as regulators of cell identity and differentiation through their interactions with lineage-specific factors. However, the role of BET proteins has not yet been investigated in melanocyte differentiation.
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, People's Republic of China.
Background: Gang goose is a native species with gray plumage in Sichuan, China. As a result of overhunting, the number of gray Gang geese has decreased dramatically. To keep the species from extinction, conservation work for Gang geese was undertaken.
