UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis.

ABSTRACT: The leading cause of cutaneous squamous cell carcinomas (cSCCs) is exposure to ultraviolet radiation (UV). Unlike most other cancers, the incidence rates of cSCCs are still on the rise and the treatment options currently available are limited. We have recently found that dihydroorotate dehydrogenase (DHODH), which is the rate-limiting enzyme in the de novo pyrimidine synthesis pathway, plays a critical role in UVB-induced energy metabolism reprogramming. Using a multistage model of UVB radiation-induced skin cancer, we show that UVB-induced DHODH upregulation is mainly regulated transcriptionally by STAT3. Our results indicate that chronic inhibition of DHODH by leflunomide (LFN) blocks UVB-induced tumor initiation. Human tumor xenograft studies showed that LFN treatment reduces growth of

SUBMITTER: Hosseini M 

PROVIDER: S-EPMC6760220 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature