IFN induces the expression of ISGs by JAK-STAT signaling pathway and inhibits malignant tumor growth, but the functions and mechanisms of most ISGs in cancer are unknown. ISG12a was expressed at low level in in HCC an...
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IFN induces the expression of ISGs by JAK-STAT signaling pathway and inhibits malignant tumor growth, but the functions and mechanisms of most ISGs in cancer are unknown. ISG12a was expressed at low level in in HCC and GC and identified as a tumor suppressor that modulates the clinical prognosis. ISG12a silencing accelerated the malignant transformation and EMT of cancer cells. ISG12a promoted the proteasomal degradation of β-catenin by inhibiting the degradation of ubiquitinated Axin, suppressing the Wnt/β-catenin pathway. β-catenin was identified to be a transcription factor for PD-L1. The inhibition of the Wnt/β-catenin signaling pathway by ISG12a suppressed the expression of PDL1, rendering cancer cells sensitive to NK cell-mediated killing. This study reveals a mechanism underlying the anticancer effects of IFN. Some ISGs, as represented by ISG12a, may hold the secrets for cancer immunotherapy and prevention.
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