Dataset Information

Histone Deacetylases Inhibit the Snail2-Mediated EMT During Metastasis of Hepatocellular Carcinoma Cells.

ABSTRACT: Snail2 has an important role in the epithelial-mesenchymal transition (EMT) and tumor metastasis. Here, we report that Snail2 is highly expressed during TGF-? induced EMT in HL-7702 cells. Additionally, overexpression of Snail2 successfully promotes the migration and invasion of these cells, both in vitro and in a mouse model. Furthermore, our results show that HDAC1 and HDAC3 could suppress the Snail2 gene promoter. Moreover, we find that the acetylation of H3K4 and H3K56 are significantly reduced during the EMT process of liver HL-7702 cells. Thus, our results indicate that HDAC1 and HDAC3 epigenetically suppress the expression of Snail2 during the EMT of liver cells, revealing an opposing function of HDACs during the migration of malignant tumors.

SUBMITTER: Hu Y

PROVIDER: S-EPMC7419474 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Histone Deacetylases Inhibit the Snail2-Mediated EMT During Metastasis of Hepatocellular Carcinoma Cells.

Hu Yue Y Nie Qing Q Dai Mingrui M Chen Fangfang F Wu Hui H

Frontiers in cell and developmental biology 20200805

Snail2 has an important role in the epithelial-mesenchymal transition (EMT) and tumor metastasis. Here, we report that Snail2 is highly expressed during TGF-β induced EMT in HL-7702 cells. Additionally, overexpression of Snail2 successfully promotes the migration and invasion of these cells, both <i>in vitro</i> and in a mouse model. Furthermore, our results show that HDAC1 and HDAC3 could suppress the Snail2 gene promoter. Moreover, we find that the acetylation of H3K4 and H3K56 are significant ...[more]

PMID: 32850856

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Project description:Rationale: Emerging evidence suggests that noncentrosomal microtubules play an essential role in intracellular transport, cell polarity and cell motility. Whether these noncentrosomal microtubules exist or function in cancer cells remains unclear. Methods: The expression and prognostic values of CAMSAP2 and its functional targets were analyzed by immunohistochemistry in two independent HCC cohorts. Immunofluorescence and co-immunoprecipitation were used for detection of CAMSAP2-decorated noncentrosomal microtubule. Chromatin immunoprecipitation and luciferase report assays were used to determine the c-Jun binding sites in HDAC6 promoter region. In vitro migration and invasion assays and in vivo orthotopic metastatic models were utilized to investigate invasion and metastasis. Results: We reported a microtubule minus‑end‑targeting protein, CAMSAP2, is significantly upregulated in hepatocellular carcinoma (HCC) and correlated with poor prognosis. CAMSAP2 was specifically deposited on microtubule minus ends to serve as a "seed" for noncentrosomal microtubule outgrowth in HCC cells. Upon depletion of CAMSAP2, the noncentrosomal microtubule array was transformed into a completely radial centrosomal pattern, thereby impairing HCC cell migration and invasion. We further demonstrated that CAMSAP2 cooperates with EB1 to regulate microtubule dynamics and invasive cell migration via Trio/Rac1 signaling. Strikingly, both immunofluorescence staining and western blotting showed that CAMSAP2 depletion strongly reduced the abundance of acetylated microtubules in HCC cells. Our results revealed that HDAC6, a promising target for cancer therapy, was inversely downregulated in HCC and uniquely endowed with tumor-suppressive activity by regulation CAMSAP2-mediated microtubule acetylation. Mechanistically, CAMSAP2 activates c-Jun to induce transrepression of HDAC6 through Trio-dependent Rac1/JNK pathway. Furthermore, NSC23766, a Rac1-specific inhibitor significantly inhibited CAMSAP2-mediated HCC invasion and metastasis. Conclusions: CAMSAP2 is functionally, mechanistically, and clinically oncogenic in HCC. Targeting CAMSAP2-mediated noncentrosomal microtubule acetylation may provide new therapeutic strategies for HCC metastasis.

Dataset Information

Histone Deacetylases Inhibit the Snail2-Mediated EMT During Metastasis of Hepatocellular Carcinoma Cells.

Publications

Histone Deacetylases Inhibit the Snail2-Mediated EMT During Metastasis of Hepatocellular Carcinoma Cells.

Similar Datasets

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