(2e-4e-6e-10e)-3-7-11-15-tetramethyl-2-4-6-10-14-hexadecapentaenoic-acid and Neoplasm-Metastasis

Hepatocellular carcinoma (HCC) is a highly lethal cancer that has a high rate of recurrence, in part because of cancer stem cell (CSC)-dependent field cancerization. Acyclic retinoid (ACR) is a synthetic vitamin A-like compound capable of preventing the recurrence of HCC. Here, we performed a genome-wide transcriptome screen and showed that ACR selectively suppressed the expression of MYCN, a member of the MYC family of basic helix-loop-helix-zipper transcription factors, in HCC cell cultures, animal models, and liver biopsies obtained from HCC patients. MYCN expression in human HCC was correlated positively with both CSC and Wnt/β-catenin signaling markers but negatively with mature hepatocyte markers. Functional analysis showed repressed cell-cycle progression, proliferation, and colony formation, activated caspase-8, and induced cell death in HCC cells following silencing of MYCN expression. High-content single-cell imaging analysis and flow cytometric analysis identified a MYCN

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Epithelial Cell Adhesion Molecule; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; N-Myc Proto-Oncogene Protein; Neoplasm Metastasis; Neoplastic Stem Cells; Prognosis; Tretinoin; Wnt Signaling Pathway