Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling

Zhang, Peng Fei; Ks, Li; Shen, Y-H.; Pt, Gao; Zr, Dong; Jb, Cai; Zhang, Chao; Xy, Huang; Mx, Tian; Zq, Hu; Dm, Gao; Fan, Jia; Ke, Ai–Wu; Gm, Shi

doi:10.1038/cddis.2015.324

Cited by 206 publications

(195 citation statements)

References 34 publications

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“…Once activated, integrins initiate the activation of FAK . It has also been recently reported that the activation of FAK facilitates EMT of HCC cells . In this study, as expected, the phosphorylation of FAK was notably inactivated in Talin1‐knockdown cells, indicating that Talin1‐mediated EMT is FAK‐independent (Fig.…”

Section: Resultssupporting

confidence: 86%

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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Section: Resultssupporting

confidence: 86%

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

et al. 2017

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“…For example, miR‐128 potently reverses metastasis and chemoresistance of highly malignant NSCLC cells, which could be completely reversed by restoring pro‐EMT signaling pathway activities, including Wnt/β‐catenin and TGF‐β (Cai et al, ). In our previous study, we reported that overexpression of galectin‐1 can induce EMT in HCC cells through activating the PI3K/AKT cascade signaling pathway, which can counteract the effect of sorafenib (Zhang et al, ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR‐128/CD151 pathway in hepatocellular carcinoma

Zhang

Wang

et al. 2018

Journal Cellular Physiology

164

135

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Dysregulation of long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and tumor progression, including hepatocellular carcinoma (HCC). Small nucleolar RNA host gene 3 (SNHG3) has been considered as an lncRNA to be associated with a poor prognosis in patients with HCC. Here, we reported that SNHG3 expression was significantly higher in the highly metastatic HCC (HCCLM3) cells compared with the lowly metastatic HCC cells (Hep3B and PLC/PRF/5). Furthermore, forced expression of SNHG3 promoted cell invasion, epithelial-mesenchymal transition (EMT), and sorafenib resistance in HCC. Moreover, SNHG3 overexpression induced HCC cells EMT via miR-128/CD151 cascade activation. Clinically, our data revealed that increased SNHG3 expression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that SNHG3 may be a novel therapeutic target and a biomarker for predicting response to sorafenib treatment of HCC.

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“…The overexpression of MMP1 22 and LGALS1 23 has been identified to correlate with poor prognosis of CRC patients, and upregulated MMP1 and LGALS1 induce the development of EMT in cancer 24, 25 . Prognostic analysis using CRC cohort from TCGA showed no prognostic significance of MMP1 (see Supplementary Figure S3), whereas our result and another study have confirmed the prognostic significance of MMP1 in CRC patients 22 .…”

Section: Discussionmentioning

confidence: 99%

The integrated pathway of TGFβ/Snail with TNFα/NFκB may facilitate the tumor-stroma interaction in the EMT process and colorectal cancer prognosis

Zhong

et al. 2017

Sci Rep

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Substantial evidence has shown that epithelial-mesenchymal transition (EMT) plays critical roles in colorectal cancer (CRC) development and prognosis. To uncover the pivotal regulators that function in the cooperative interactions between cancer cells and their microenvironment and consequently affect the EMT process, we carried out a systematic analysis and evaluated prognosis in CRC specimens. Tumor buds and their surrounding stroma were captured using laser microdissection. We used gene expression profiling, bioinformatics analysis and regulatory network construction for molecular selection. The clinical significance of potential biomarkers was investigated. We identified potential EMT biomarkers, including BGN, MMP1, LGALS1, SERPINB5, and TM4SF4, all of which participated in the integrated pathway of TGFβ/Snail with TNFα/NFκB. We also found that BGN, MMP1, LGALS1, SERPINB5 and TM4SF4 were related to CRC patient prognosis. Patients with higher expression of these individual potential biomarkers had poorer prognosis. Among the identified biomarkers, BGN and TM4SF4 are reported, for the first time, to probably be involved in the EMT process and to predict CRC prognosis. Our results strongly suggest that the integrated pathway of TGFβ/Snail with TNFα/NFκB may be the principal axis that links cancer cells to their microenvironment during the EMT process and results in poor prognosis in CRC patients.

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Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling

Cited by 206 publications

References 34 publications

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

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

LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR‐128/CD151 pathway in hepatocellular carcinoma

The integrated pathway of TGFβ/Snail with TNFα/NFκB may facilitate the tumor-stroma interaction in the EMT process and colorectal cancer prognosis

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