ELENA GOMEZ ABENZA¹, Sofía Ibañez Molero², DIANA GARCIA MORENO³, Inmaculada Fuentes Martínez³, Leonard I Zon⁴, Maria Caterina Mione⁵, MARIA LUISA CAYUELA FUENTES⁶, Chiara Gabellini², Victoriano Mulero Méndez³

(1) [GI/IMIB/C003/2011] CIRUGÍA DIGESTIVA, ENDOCRINA Y TRASPLANTE DE ÓRGANOS ABDOMINALES, IMIB-Arrixaca, España and University of Navarra, Center of Applied Medical Research (CIMA), IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain., 30100, España (Región de Murcia)
(2)
(3) INMUNIDAD, INFLAMACIÓN Y CÁNCER, IMIB, España
(4) Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA, Estados Unidos
(5) Laboratory of Experimental Cancer Biology, Cibio, University of Trento, Trento, Italy, Italia
(6) CIRUGÍA DIGESTIVA, ENDOCRINA Y TRASPLANTE DE ÓRGANOS ABDOMINALES, IMIB, España

PMID: 31519199
Referencia: Gómez-Abenza E, Ibáñez-Molero S, García-Moreno D, Fuentes I, Zon LI, Mione MC, Cayuela ML, Gabellini C, Mulero V. Zebrafish modeling reveals that SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment. J Exp Clin Cancer Res. 2019 Sep 13;38(1):405. doi: 10.1186/s13046-019-1389-3. PubMed PMID: 31519199; PubMed Central PMCID: PMC6743187.
ISSN: 1756-9966
Revista:
Factor de impacto (2017):
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Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancer and while incidence rates are declining for most cancers, they have been steadily rising for SKCM. 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, such as squamous cell carcinoma and colorectal cancer.

We used the unique advantages of the zebrafish to model the impact of Spint1a deficiency in early transformation, progression and metastatic invasion of SKCM together with in silico analysis of the occurrence and relevance of SPINT1 genetic alterations of the SKCM TCGA cohort.

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. The zebrafish model reveals 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 reveal a novel therapeutic target for SKCM.