EDIL3 is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma

Xia, Hongping; Chen, Jianxiang; Shi, Ming; Gao, Hengjun; Sekar, Karthik; Seshachalam, Veerabrahma Pratap; Ooi, London Lucien; Hui, Kam M.

doi:10.1016/j.jhep.2015.05.005

Cited by 72 publications

(66 citation statements)

References 32 publications

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“…EGF‐like repeat and discoidin I‐like domain‐containing protein 3 (EDIL3) induced EMT and promoted hepatocellular carcinoma migration, invasion, and angiogenesis in vitro . Furthermore, the overexpression of EDIL3 induced the activation of ERK and TGF‐β signaling, and the deletion of EDIL3 suppressed EMT in lens epithelial cells through the TGF‐β signaling pathway .…”

Section: Small Molecules Against Emtmentioning

confidence: 99%

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

104

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Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.

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Section: Small Molecules Against Emtmentioning

confidence: 99%

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

104

View full text Add to dashboard Cite

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“…By comparing with our established global gene expression profile database of human HCC, 67 many genes, which are prominently downregulated by Pt-NA, are those known to be highly expressed in liver cancer (Table S1). Ingenuity pathway analysis (IPA) demonstrates that Pt-NA mainly modulates genes related to the cell cycle and DNA damage-related pathways (Figures S22 and S23).…”

Section: Resultsmentioning

confidence: 99%

pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma

et al. 2016

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Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide. Pt-NA is latent in peripheral blood, readily targets disseminated HCC CSLCs, and disassembles into small Pt nanoclusters in acidic subcellular compartments, eventually inducing damage to DNA. Furthermore, treatment with Pt-NA downregulates a multitude of genes that are vital for the proliferation of HCC. Importantly, CD24+ side population (SP) CSLCs that are resistant to cisplatin are sensitive to Pt-NA, demonstrating the immense potential of Pt-NA for treating chemoresistant HCC.

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“…a). Hence, to clarify the molecular basis of the promoting effects of Talin1 knockdown on HCC cell EMT, we assessed the activation of several signaling pathways, including the transforming growth factor‐β, Smad2/3, phosphatidylinositol 3‐kinase, AKT, Rho family, and ERK1/2 pathways, which have been known to be involved in the induction of EMT . Among the screened pathways, phosphorylated ERK1/2 was significantly elevated in Talin1‐knockdown cells, whereas phosphorylated Smad2/3, phosphorylated AKT, RhoA, and Rac1 showed no such changes (Fig.…”

Section: Resultsmentioning

confidence: 99%

Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway

et al. 2017

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Talin1 is an adaptor protein that conjugates integrins to the cytoskeleton and regulates integrins and focal adhesion signaling. Several studies have found that Talin1 is overexpressed in several tumor types and promotes tumor progression. However, the explicit role of Talin1 in hepatocellular carcinoma (HCC) progression is still unclear and its functional mechanism remains largely unknown. In this study, we showed a trend of gradually decreasing expression of Talin1 from normal liver tissues to hepatocirrhosis, liver hyperplasia, the corresponding adjacent non‐tumor, primary HCC, and eventually metastatic foci, indicating that Talin1 may correlate with HCC initiation to progression. Talin1 was significantly downregulated in HCC tissues compared with adjacent non‐tumor tissues and low Talin1 expression was associated with HCC progression and poor prognosis. Furthermore, Talin1 knockdown induced epithelial–mesenchymal transition and promoted migration and invasion in SK‐Hep‐1 cells and HepG2 cells. Mechanistically, we found that the ERK pathway was responsible for these promoting effects of Talin1 knockdown in HCC cells. The promoting effects of Talin1 knockdown on epithelial–mesenchymal transition, migration, and invasion were reversed by U0126, a specific ERK1/2 inhibitor. Taken together, our results suggested that Talin1 might serve as a tumor suppressor in HCC and a potential prognostic biomarker for HCC patients.

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EDIL3 is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma

Cited by 72 publications

References 32 publications

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma

Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway

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