RT Journal Article
SR Electronic
T1 SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 611145
DO 10.1101/611145
A1 Elena Gómez-Abenza
A1 Sofía Ibáñez-Molero
A1 Diana García Moreno
A1 Inmaculada Fuentes
A1 Leonard I. Zon
A1 Maria C. Mione
A1 María L. Cayuela
A1 Chiara Gabellini
A1 Victoriano Mulero
YR 2019
UL http://biorxiv.org/content/early/2019/04/16/611145.abstract
AB 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 nonautonomous levels to enhance invasiveness of SKCM. These results suggest the relevance of clinical intervention on this signaling pathway for precision SKCM medicine.Summary statement A zebrafish model shows that Spint1a deficiency facilitates oncogenic transformation, regulates the tumor/immune microenvironment crosstalk, accelerates the onset of SKCM, and promotes metastatic invasion in cell autonomous and non-autonomous manners.