A Positive TGF-β/c-KIT Feedback Loop Drives Tumor Progression in Advanced Primary Liver Cancer.

ABSTRACT:

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Hepatocellular carcinoma (HCC) is globally the second most common cause of cancer mortality. The majority of HCC patients are diagnosed at advanced stage disease for which no curative treatments exist. TGF-β has been identified as a potential therapeutic target. However, the molecular mechanisms mediating its functional switch from a tumor suppressor to tumor promoter in HCC and its interactions with other signaling pathways are poorly understood. Here, we demonstrate an aberrant molecular network between the TGF-β and c-KIT pathway that mediates the functional switch of TGF-β to a driver of tumor progression in HCC. TGF-β/SMAD2 signaling transcriptionally regulates expression of the c-KIT receptor ligand (stem cell factor [SCF]) with subsequent auto- and paracrine activ

SUBMITTER: Rojas A 

PROVIDER: S-EPMC4909706 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature