Actions of free ISG15 in some cancer types

Cancer typeActionsReference
PDATAMS from patients with PDA exhibits a high ISG15 expression. TAM secretes ISG15, increasing the phenotype of CSCs. Moreover, IFN-β promotes that CSCs also secrete ISG15[62]
MelanomaSoluble ISG15 is secreted to medium from melanoma cells, promoting E–cadherin expression on human dendritic cells[63]

Patients with ESCC have increased ISG15 expression

High levels of free ISG15 are found in the plasma of patients with ESCC compared with healthy patients

Breast cancer

Exogenous-free ISG15 reduces tumor growth in athymic mice by promoting NK cell infiltration

Intracellular-free ISG15 promotes the expression of MHCI

OSCCFree ISG15 interacts with Rac1-GDP, promoting cell migration in an ISGylation-independent manner. This event has been related to lymphatic metastasis of OSCC[66]

PDA: pancreatic ductal adenocarcinoma; TAMs: tumor-associated macrophages; ESCC: esophageal squamous cell carcinoma; MHCI: major histocompatibility complex I; OSCC: oral squamous cell carcinoma; CSCs: cancer stem cells