Dual inhibition of EGFR and c-Met kinase activation by MJ-56 reduces metastasis of HT29 human colorectal cancer cells

Chen, Hui-Jye; Jiang, Yilin; Lin, Chung-Ming; Tsai, Shih‐Chang; Peng, Shu‐Fen; Fushiya, Shinji; Hour, Mann‐Jen; Yang, Jai Sing

doi:10.3892/ijo.2013.1941

Cited by 23 publications

(17 citation statements)

References 70 publications

(88 reference statements)

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“…In line with our findings, downregulation of p-rpS6 are also attenuated the cells invasion in esophageal squamous cell carcinoma [ 18 ] and renal angiomyolipoma [ 7 ]. MJ-56, a new novel anti-metastasis drug, even showed the p-rpS6-mediated invasion inhibition effects in colorectal cancer cells [ 53 ]. These results imply that p-rpS6 might be importantly involved in multiple cells invasion and its overexpression will probably facilitate the tumors aggressiveness to a large extent.…”

Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer

Chen

Tan

Gao

et al. 2015

J Exp Clin Cancer Res

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BackgroundRibosomal protein S6 (rpS6), a component of the 40S ribosomal subunit, is involved in multiple cellular bioactivities. However, its clinicopathological significance in non-small cell lung cancer (NSCLC) is poorly understood.MethodsExpressions of total rpS6 (t-rpS6) and phosphorylated rpS6 (Ser235/236, p-rpS6) were detected immunohistochemically in 316 NSCLC tissues and 82 adjacent controls, followed by statistical evaluation of the relationship between proteins expressions and patients’ survivals to identify their prognostic values. Cytological experiments with overexpressing or silencing rpS6 by lentivirus in human bronchial epithelial (HBE) and NSCLC cell lines were performed to explore potential mechanisms by which rpS6 affects the clinical development of NSCLC. Additionally, specific RNA interference for Akt1, Akt2, Akt3, Akt inhibitor and subsequent cellular bioactivity tests were employed as well to investigate the upstream regulation of rpS6.ResultsPositive rates of t-rpS6 and p-rpS6 were both significantly increased in NSCLC tissues, compared with controls (82.91 vs 62.20 % for t-rpS6; 52.22 vs 21.95 % for p-rpS6; both P < 0.001). However, only hyperphosphorylation of rpS6, expressed as either elevated p-rpS6 alone or the ratio of p-rpS6 to t-rpS6 (p-rpS6/t-rpS6) no less than 0.67, was greatly associated with the unfavorable survival of NSCLC patients, especially for cases at stage I (all P < 0.001). The independent adverse prognostic value of hyperphosphorylated rpS6 was confirmed by multivariate Cox regression analysis (hazard ratios for elevated p-rpS6 alone and p-rpS6/t-rpS6 no less than 0.67 were 2.403, 4.311 respectively, both P < 0.001). Overexpression or knockdown of rpS6, along with parallel alterations of p-rpS6, led to increased or decreased cells proliferations respectively, which were dependent on redistributions of cell cycles (all P < 0.05). Cells migration and invasion also changed with rpS6 interference (all P < 0.05). Furthermore, upstream overexpression or knockdown of Akt2 or Akt2 phosphorylation inhibition, rather than Akt1 or Akt3, resulted in striking hyperphosphorylation or dephosphorylation of mTOR, p70S6K and rpS6 (all P < 0.05), without any change in total proteins expressions. Further tests showed markedly accompanied variation of cells proliferation, cell cycle distribution and invasion (all P < 0.05).ConclusionHyperphosphorylation of rpS6, probably regulated by the Akt2/mTOR/p70S6K signaling pathway, is closely relevant to the progression of NSCLC and it might be served as a promising therapeutic target for NSCLC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0239-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer

Chen

Tan

Gao

et al. 2015

J Exp Clin Cancer Res

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“…It is well documented that cell metastasis is one of the major causes of colorectal cancer-related mortality (17,18,30). Interference with human epidermal growth factor receptor (EGFR) or downstream intracellular signaling provides a novel approach in cancer chemotherapeutic agents (31)(32)(33). Activation of the EGFR pathway promotes by EGF-stimulated responsible for colorectal cancer cell growth, invasion, metastasis and inhibition of cell death (34,35).…”

Section: Discussionmentioning

confidence: 99%

Allyl isothiocyanate inhibits cell metastasis through suppression of the MAPK pathways in epidermal growth factor-stimulated HT29 human colorectal adenocarcinoma cells

Lai

Tang

et al. 2013

Oncology Reports

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Allyl isothiocyanate (AITC) has been found to present sources from consumed cruciferous vegetables. AITC is known to possess pharmacological and anticancer activities. The present study was designed to test the hypothesis that AITC suppressed the invasion and migration of epidermal growth factor (EGF)-stimulated HT29 cells and to elucidate the mechanisms for the antimetastatic abilities in vitro. The invasion and migration of EGF-stimulated HT29 cells were determined individually by Transwell cell invasion and wound-healing assays. Our results showed that AITC effectively inhibited both the invasive and migratory ability of HT29 cells. Furthermore, AITC downregulated the protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and mitogen-activated protein kinases (MAPKs) (p-JNK, p-ERK and p-p38) by western blot analysis in HT29 cells following EGF induction. Thus, the metastatic responses in AITC-treated HT29 cells after EGF stimulation were mediated by the MMP-2/-9 and MAPK signaling pathways. We also used gene expression microarrays to investigate the gene levels related to cell growth, G-protein coupled receptor, angiogenesis, cell adhesion, cell cycle and mitosis, cell migration, cytoskeleton organization, DNA damage and repair, transcription and translation, EGFR and PKB/mTOR signals. In summary, it is possible that AITC suppresses the invasion and migration of EGF-induced HT29 cells, resulting from MMP-2/-9 and MAPKs. Hence, AITC may be beneficial in the treatment of human colorectal adenocarcinoma in the future.

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“…They have proven that MJ‐56 can inhibit invasion and migration of HT29 cells by targeting EGFR and c‐MET, and therefore ERK and PI3K/AKT/mTOR signaling. The blocking of matrix metalloproteinases is due to inhibition of the NF‐kB signaling pathway . Hu et al used curcumin on DU145 cell lines, and have shown that curcumin can suppress HGF‐induced effects that included upregulation of vimentin and downregulation of E‐cadherin.…”

Section: The Therapeutic Targeting C‐met/hgf Signaling Pathway In Crcmentioning

confidence: 99%

The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer

et al. 2019

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Colorectal cancer (CRC) is the third most common cancer and a common cause of cancer‐related mortality globally. In spite of the improvements in the early diagnosis of CRC, approximately one‐third of patients develop metastasis and then have a very poor survival rate. The mesenchymal–epithelial transition factor (c‐MET) is a tyrosine kinase cell surface receptor activated by hepatocyte growth factor (HGF). Activation of c‐MET/HGF signaling pathway regulates a variety of biological processes including cell motility, cell proliferation, angiogenesis, the epithelial‐to‐mesenchymal transition, and the development and progression of cancer cells. Recent studies have suggested that the c‐MET/HGF signaling pathway is involved in the carcinogenesis of CRC. In this review, we summarize the main findings of recent studies investigating the role of c‐MET/HGF signaling pathway in CRC and the potential of the c‐MET/HGF signaling pathways in the diagnosis and treatment of CRC. © 2019 IUBMB Life, 2019

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Dual inhibition of EGFR and c-Met kinase activation by MJ-56 reduces metastasis of HT29 human colorectal cancer cells

Cited by 23 publications

References 70 publications

Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer

Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer

Allyl isothiocyanate inhibits cell metastasis through suppression of the MAPK pathways in epidermal growth factor-stimulated HT29 human colorectal adenocarcinoma cells

The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer

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