SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment

SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment

Publication date: Apr 17, 2019

Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer and while incidence rates are declining for most cancers, they have been steadily rising for SKCM worldwide. Serine protease inhibitor, kunitz-type, 1 (SPINT1) is a type II transmembrane serine protease inhibitor that has been shown to be involved in the development of several types of cancer. We report here a high prevalence of SPINT1 genetic alterations in SKCM patients and their association with altered tumor immune microenvironment and poor patient survival. We used the unique advantages of the zebrafish to model the impact of SPINT1 deficiency in early transformation, progression and metastatic invasion of SKCM. Our results reveal that Spint1a deficiency facilitates oncogenic transformation, regulates the tumor/immune microenvironment crosstalk, accelerates the onset of SKCM and promotes metastatic invasion. Notably, Spint1a deficiency is required at both cell autonomous and non-autonomous levels to enhance invasiveness of SKCM. These results suggest the relevance of clinical intervention on this signaling pathway for precision SKCM medicine.

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Concepts Keywords
Benaud Http
Boston Transplantation
Breast Html
Brennero Stem cells
Cambridge Cloning
Cancer Invasion
Cervix API
Correlation Carcinogenesis
Crosstalk Neoplasm
Dana Farber Cancer pathology
Drug Resistance Zebrafish
Endogenous Melanoma
Epidermal Oncology
Epidermis Clinical medicine
Epithelial Mesenchymal Transition RTT
Esophagus Medical specialties
Etiology Medicine
Exogenous Imaging
Friction
Genetic
Genetic Heterogeneity
Harvard
Hematology
Hepatocyte Growth Factor
Howard Hughes
Immunosuppression
Incidence
Inflammation
Inhibitor
Interplay
Italy
Keratin
Keratinocytes
Liver
Macrophages
Mail
Malignancy
Malignant Transformation
Medicine
Melanocytes
Melanoma
Metastasis
Metastasized
Metastatic
Microenvironment
Multigenic
Murcia
Mutant
Mutation
Neural Crest
Neutrophil
NIH
Oncogenic
Osteomyelitis
Ovaries
Perpetuity
Phenotype
Pigment
Pisa
Prostate
Proteolytic
Serine Protease Inhibitor
Sinuses
Spain
Stroma
Transgenic
Transmembrane
Trauma
Trento
Tumor
Tumorigenesis
Ulcers
Universitario
Vivo
Zebrafish

Semantics

Type Source Name
gene UNIPROT FOXG1
drug DRUGBANK Spinosad
gene UNIPROT BRD2
gene UNIPROT CXCL2
gene UNIPROT KIT
disease MESH death
gene UNIPROT CNTN3
gene UNIPROT SOAT1
gene UNIPROT COL9A3
gene UNIPROT COMP
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SCN8A
gene UNIPROT MBNL1
drug DRUGBANK Rasagiline
drug DRUGBANK Trypsin
gene UNIPROT NSMAF
gene UNIPROT CNTRL
gene UNIPROT CXCR1
gene UNIPROT CXCL8
gene UNIPROT INTU
drug DRUGBANK Serine
gene UNIPROT FATE1
gene UNIPROT NR4A3
gene UNIPROT MMUT
gene UNIPROT PIK3CA
gene UNIPROT SIM2
gene UNIPROT MLC1
gene UNIPROT SERPINB13
drug DRUGBANK Hyaluronic acid
gene UNIPROT COX5A
gene UNIPROT COX8A
gene UNIPROT CPOX
gene UNIPROT TNFRSF11A
disease MESH multiple
gene UNIPROT NOVA2
gene UNIPROT RPS11
gene UNIPROT PRDM6
disease DOID dish
gene UNIPROT TANK
drug DRUGBANK Water
pathway BSID Fertilization
drug DRUGBANK Perchlorate
drug DRUGBANK Ciclosporin
gene UNIPROT IDO1
gene UNIPROT CES2
gene UNIPROT CASP1
gene UNIPROT TSPO
gene UNIPROT CHRM3
gene UNIPROT TUBE1
gene UNIPROT FBXO8
gene UNIPROT FBRS
gene UNIPROT WASHC1
drug DRUGBANK Streptomycin
drug DRUGBANK Benzylpenicillin
gene UNIPROT F12
disease MESH fungal infections
gene UNIPROT SERPINF2
drug DRUGBANK Alpha-1-proteinase inhibitor
drug DRUGBANK Ethanol
drug DRUGBANK Isoflurane
gene UNIPROT TNFSF14
gene UNIPROT ARID1A
gene UNIPROT NDE1
disease DOID intestinal tumors
disease DOID squamous carcinoma
disease MESH squamous carcinoma
pathway BSID Angiogenesis
gene UNIPROT MX2
gene UNIPROT B2M
gene UNIPROT MPEG1
gene UNIPROT LYZ
gene UNIPROT IL1B
gene UNIPROT CDH1
gene UNIPROT FZR1
gene UNIPROT SNAI2
gene UNIPROT MMP9
gene UNIPROT SLC35G1
drug DRUGBANK Aspartame
gene UNIPROT CFLAR
gene UNIPROT SH3PXD2A
gene UNIPROT HRAS
gene UNIPROT LGALS4
gene UNIPROT CD163
gene UNIPROT MFAP4
gene UNIPROT CXCR2
gene UNIPROT TNFRSF1A
gene UNIPROT TNF
gene UNIPROT TWIST2
gene UNIPROT TWIST1
gene UNIPROT ZEB2
gene UNIPROT ZEB1
gene UNIPROT SLC22A3
gene UNIPROT ITK
disease MESH diagnosis
gene UNIPROT DCT
gene UNIPROT TYR
drug DRUGBANK L-Tyrosine
gene UNIPROT SOX10
gene UNIPROT LARGE1
pathway BSID Macrophage markers
gene UNIPROT STIM1
disease DOID TAM
gene UNIPROT SPG21
gene UNIPROT SPACA9
pathway BSID Extracellular matrix organization
pathway BSID Immune System
disease MESH nevus
disease DOID skin inflammation
disease MESH liver cancers
disease MESH tumorigenesis
gene UNIPROT HGFAC
gene UNIPROT ST14
disease MESH infections
gene UNIPROT RPS4X
disease DOID osteomyelitis
disease MESH osteomyelitis
disease MESH ulcers
disease MESH scars
disease MESH dysplastic nevi
gene UNIPROT SMIM10L2A
gene UNIPROT SMIM10L2B
gene UNIPROT ENG
disease MESH recurrence
gene UNIPROT TNIP1
gene UNIPROT MAGEE1
gene UNIPROT LRP1
gene UNIPROT PMAIP1
disease MESH metastasis
disease MESH inflammation
disease DOID melanoma
pathway BSID Developmental Biology
gene UNIPROT NFKBIZ
disease DOID cancer
gene UNIPROT IMPACT
disease MESH development
disease DOID skin cancer
disease MESH skin cancer
pathway BSID Melanoma
disease MESH SKCM
disease MESH tumor
disease DOID cutaneous melanoma
gene UNIPROT SPINT1

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