title: Apicidin-resistant HA22T hepatocellular carcinoma cells strongly activated the Wnt/β-catenin signaling pathway and MMP-2 expression via the IGF-IR/PI3K/Akt signaling pathway enhancing cell metastatic effect.
abstract: The IGF-IR/PI3K/Akt signaling pathway inhibited GSK3-β activity by phosphorylation and this promoted β-catenin nuclear localization. Our previous study indicated that β-catenin mRNA level was significantly higher in tumor areas than in non-tumor ones, especially in late pathologic stage tumors. However, β-catenin inhibition resulted in significantly suppressed migration and invasion ability of HA22T cells. Thus, Wnt/β-catenin pathway over-activation might be involved in metastatic enhancement of apicidin-resistant HA22T cell metastasis. Apicidin-resistant (AR) HA22T cells showed higher β-catenin nuclear accumulation and significantly decreased GSK-3-β protein level, in relation to parental cells. Results also indicated that AR cells increased abundantly in Tbx3, a downstream target of Wnt/β-catenin that it is implicated in liver cancer. AR cells also inhibited the MEK/ERK/PEA3 pathway which promoted MMP-2 activation. But, apicidin-resistant effect was totally reversed by LY294002 and AG1024. In conclusion, Apicidin-R HA22T cells activated the Wnt/β-catenin pathway and induced, MMP-2 expression via IGF-IR/PI3K/Akt signaling further enhancing cell the metastatic effects.
authors: Department of Health and Nutritional Biotechnology, Asia University.
authors: Cheng-Hong
authors: CH
authors: Hsieh
authors: Li-Hao
authors: LH
authors: Cheng
authors: Hsi-Hsien
authors: HH
authors: Hsu
authors: Tsung-Jung
authors: TJ
authors: Ho
authors: Chuan-Chou
authors: CC
authors: Tu
authors: Yueh-Min
authors: YM
authors: Lin
authors: Ming-Cheng
authors: MC
authors: Chen
authors: Fuu-Jen
authors: FJ
authors: Tsai
authors: You-Liang
authors: YL
authors: Hsieh
authors: Chih-Yang
authors: CY
authors: Huang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010456:Peptides, Cyclic / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D010456:Peptides, Cyclic; D051153:Wnt Proteins; C102351:apicidin; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2