Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer

Toiyama, Yuji; Yasuda, Hiromi; Saigusa, Susumu; Tanaka, Kouji; Inoue, Yasuhiro; Goel, Ajay; Kusunoki, Masato

doi:10.1093/carcin/bgt282

Cited by 131 publications

(120 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, we observed a role for HIF-1a in BAG3-regulated VEGF and MMP2 expression which was consistent with previous reports that HIF-1a promotes VEGF and MMP2 expression, enhancing angiogenesis and metastasis of HCC. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Moreover, BAG3 regulated angiogenesis of HCC cells through ERK phosphorylation, in accordance with previous studies. 12 Earlier work showed that autophagy-related genes could downregulate angiogenesis; 18,19 however, in our study, knockdown of BAG3 could downregulate the autophagy process.…”

Section: Bag3 Function In Human Hepatocellular Carcinomasupporting

confidence: 91%

“…[25][26][27][28][29][30][31][32] Slug is one of the potential predictive biomarkers for identifying patients with lymph-node metastasis in colorectal cancer. 33 Moreover, BAG3 expression levels were significantly higher in HCC with portal vein-emboli and metastasis in our clinical analysis, and upregulation of slug in tissue in conjunction with an increase in BAG3 could reflect that cross-talk between BAG3 and EMT occurs in human HCC. Combined with no evident correlation between E-cadherin, N-cadherin, or vimentin with BAG3 in clinical HCC samples, it is likely that BAG3-induced metastasis is independent of slug expression.…”

Section: Bag3 Function In Human Hepatocellular Carcinomamentioning

confidence: 58%

See 1 more Smart Citation

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Xiao

Cheng

Tong

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

Bcl2-associated athanogene 3 (BAG3) protein is a co-chaperone of heat-shock protein (Hsp) 70 and may regulate major physiological and pathophysiological processes. However, few reports have examined the role of BAG3 in human hepatocellular carcinoma (HCC). In this study, we show that BAG3 regulates epithelial-mesenchymal transition (EMT) and angiogenesis in HCC. BAG3 was overexpressed in HCC tissues and cell lines. BAG3 knockdown resulted in reduction in migration and invasion of HCC cells, which was linked to reversion of EMT by increasing E-cadherin expression and decreasing N-cadherin, vimentin and slug expression, as well as suppressing matrix metalloproteinase 2 (MMP-2) expression. In a xenograft tumorigenicity model, BAG3 knockdown effectively inhibited tumor growth and metastasis through reduction in CD34 and VEGF expression and reversal of the EMT pathway. In conclusion, BAG3 is associated with the invasiveness and angiogenesis in HCC, and the BAG3 gene may be a novel therapeutic approach against HCC.

show abstract

Section: Bag3 Function In Human Hepatocellular Carcinomasupporting

confidence: 91%

Section: Bag3 Function In Human Hepatocellular Carcinomamentioning

confidence: 58%

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Xiao

Cheng

Tong

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Elevated expression of several EMT transcription factors has been considered as biomarker for lymph node metastasis (LNM) and poor prognosis in many human cancers including breast cancer 41,42 . The marked influence of PYK2 on the expression level of EMT transcription factors in MDA-MB-468 and BT-549 cells (Fig.…”

Section: Elevated Pyk2 Expression Enhances Emt In Mammary Cellsmentioning

confidence: 99%

PYK2 sustains endosomal-derived receptor signalling and enhances epithelial-to-mesenchymal transition

et al. 2015

View full text Add to dashboard Cite

Epithelial-to-mesenchymal transition (EMT) is a central developmental process implicated in cancer metastasis. Here we show that the tyrosine kinase PYK2 enhances cell migration and invasion and potentiates EMT in human breast carcinoma. EMT inducer, such as EGF, induces rapid phosphorylation of PYK2 and its translocation to early endosomes where it co-localizes with EGFR and sustains its downstream signals. Furthermore, PYK2 enhances EGF-induced STAT3-phosphorylation, while phospho-STAT3 directly binds to PYK2 promoter and regulates PYK2 transcription. STAT3 and PYK2 also enhance c-Met expression, while c-Met augments their phosphorylation, suggesting a positive feedback loop between PYK2-STAT3-c-Met. We propose that PYK2 sustains endosomal-derived receptor signalling and participates in a positive feedback that links cell surface receptor(s) to transcription factor(s) activation, thereby prolonging signalling duration and potentiating EMT. Given the role of EMT in breast cancer metastasis, we also found a significant correlation between PYK2 expression, tumour grade and lymph node metastasis, thus, demonstrating the clinicopathological implication of our findings.

show abstract

“…Following surgery, the 5-year survival rate of patients with early-stage colorectal cancer is >90%, however, the 5-year survival rate of advanced-stage patients is <10% (6). Although several genes associated with lymph node metastasis have been reported, the molecular mechanisms of early-stage metastasis in colorectal cancer remain unclear (7)(8)(9). Thus, the identification of bio-markers associated with lymph node metastasis of colorectal cancer will benefit clinical evaluation and future treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Effects of autophagy regulation of tumor-associated macrophages on radiosensitivity of colorectal cancer cells

Shao

Zhu

Chen

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Tumor-associated macrophages (TAMs), a major component of the tumor microenvironment, are crucial to the processes of tumor growth, infiltration and metastasis, and contribute to drug resistance. The importance of TAMs in radiation resistance of colorectal cancer remains unclear. To investigate the effects of autophagy regulation of TAMs on the radiosensitivity of colorectal cancer cells, the current study induced TAM formation from THP-1 monocyte cells. Sequential treatment of THP-1 cells with PMA for 72 h and human recombinant interleukin-4 for 24 h was used to stimulate THP-1 differentiation to TAMs. Expression of the cell surface markers CD68, CD204 and CD206, and changes to cell morphology were used to confirm successful differentiation. The TAMs were stimulated to promote or inhibit autophagy during co-culture with LoVo colorectal adenocarcinoma cells. The cells were irradiated, with subsequent measurement of LoVo colony formation and apoptosis. Additionally, the expression of p53, Bcl-2, survivin and Smac proteins was assessed by western blotting. Monodansylcadaverin staining was used to analyze the presence of autophagic vacuoles in TAM, and western blot analysis was used to assess the expression of Beclin-1, LC3B I and II, ATG-3, -5 and -7. The results demonstrated TAM autophagy to be markedly altered by rapamycin and bafilomycin A1 treatment. Following co-culture with TAMs, the colony formation rate and survival fraction of LoVo cells were significantly higher than those in the control group (P<0.05). It was further demonstrated that the regulation of autophagy in TAMs was able to inhibit the colony formation of LoVo colorectal cancer cells. Upregulation of TAM autophagy using rapamycin exhibited more effective inhibition of LoVo colony formation than autophagy downregulation. Notably, apoptosis was significantly increased in LoVo cells when co-cultured with TAMs only, or with rapamycin-mediated autophagy upregulated TAMs, compared with LoVo cells cultured alone (P<0.01). Expression of Bcl-2, survivin and p53 were reduced in LoVo cells co-cultured with TAMs, compared with the control group (P<0.05), whereas Smac expression was increased in the co-culture groups (P<0.01). It was demonstrated that rapamycin-mediated autophagy stimulation in TAMs led to reduced expression levels of survivin and Bcl-2, however, Smac expression was increased. The upregulation of autophagy in TAMs inhibited proliferation and induced apoptosis in colon cancer cells, and altered the expression of radiosensitivity-associated proteins. This data indicated that the radiosensitivity of colorectal cancer cells is associated with autophagy of TAM, and that stimulating TAM autophagy may increase the radiosensitivity of colorectal cancer cells.

show abstract

Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer

Cited by 131 publications

References 33 publications

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

PYK2 sustains endosomal-derived receptor signalling and enhances epithelial-to-mesenchymal transition

Effects of autophagy regulation of tumor-associated macrophages on radiosensitivity of colorectal cancer cells

Contact Info

Product

Resources

About