Shanghai Colorectal Cancer Research Center

Shanghai, China

Shanghai Colorectal Cancer Research Center

Shanghai, China

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Wang G.,Shanghai JiaoTong University | Wang G.,Shanghai Colorectal Cancer Research Center | Shen W.,Shanghai JiaoTong University | Shen W.,Shanghai Colorectal Cancer Research Center | And 18 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2017

Purpose: To study the expression and intracellular localization of phosphorylase kinase β (PHKβ) protein in colorectal cancers (CRCs), analyze its correlation with clinicopathological features and prognosis, and study the biological roles and mechanism-of-action of PHKβ in CRC cell lines. Methods: Quantitative polymerase chain reaction (qPCR) and western blot assays were performed to compare the expressions of PHKβ mRNA and protein in CRC tissues and matched normal mucosa. Tissue microarrays and immunohistochemical staining were performed to detect the expression and intracellular location of PHKβ protein and analyze its correlation with the clinicopathological characteristics and prognosis in CRC patients. Proliferation, cell cycle, wound healing, and xenograft models were used to elucidate the potential role of PHKβ in vitro and in vivo. Results: PHKβ mRNA and protein were found to be overexpressed in CRC tissue compared to the levels in normal mucosa. Positive expression of PHKβ was significantly correlated with TNM stage and distal metastasis, and elevated expression of PHKβ was an independent prognostic factor in patients with CRC. PHKβ knockdown impaired proliferation of CRC in vitro and in vivo and induced cell cycle arrest. Conclusions: PHKβ affects CRC cell growth and represents a novel prognostic biomarker. © 2017 Springer-Verlag Berlin Heidelberg


Liu Y.,Shanghai JiaoTong University | Liu Y.,Shanghai Colorectal Cancer Research Center | Wang G.,Shanghai JiaoTong University | Wang G.,Shanghai Colorectal Cancer Research Center | And 14 more authors.
Oncogene | Year: 2016

Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development and progression, we investigated its downstream transcription factor TEAD4 in colorectal cancer (CRC). Increased expression and nuclear localization of TEAD4 were found in a significant portion of CRC tissues, in association with metastasis and a poor prognosis. In CRC cells, TEAD4 knockdown induced the mesenchymal-epithelial transition and decreased cell mobility in vitro and metastasis in vivo. Microarray analysis revealed that TEAD4 promoted cell adhesion and upregulated the epithelial-mesenchymal transition-related transcriptome in CRC cells. Vimentin was identified as a new direct target gene mediating TEAD4 function in CRC cells, whereby forced vimentin expression markedly reversed TEAD4-knockdown-induced cell morphological changes and decreased mobility. Interestingly, rescued expression of both WT TEAD4 and a Y429H mutant can reverse the mesenchymal-epithelial transition and increase vimentin expression, cell mobility and metastatic potential in TEAD4-knockdown CRC cells. The discrepant expression of YAP and TEAD4 in CRC tissues, the rescue ability of TEAD4 mutant defect in YAP binding and no effect on vimentin expression by YAP knockdown in CRC cells, all implicated a YAP-independent manner of TEAD4 function in CRC. Furthermore, vimentin positively correlated and CDH1 reversely correlated with the level of TEAD4 in CRC tissues and xenograft tumors. Our results suggest that TEAD4 nuclear expression can serve as a biomarker for CRC progression and poor prognosis. The transcription factor TEAD4 regulates a pro-metastasis transcription program in a YAP-independent manner in CRC, thus providing a novel mechanism of TEAD4 transcriptional regulation and its oncogenic role in CRC, independently of the Hippo pathway. © 2016 Macmillan Publishers Limited. All rights reserved.


Zhu Y.,Yangzhou University | Xu A.,Yangzhou University | Li J.,Shanghai JiaoTong University | Li J.,Shanghai Colorectal Cancer Research Center | And 10 more authors.
Cancer Biomarkers | Year: 2016

BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related death around the world. MicroRNAs (miRNAs) are small non-coding RNAs that often are abnormally expressed in tumors. Detection and quantitation of miRNAs may provide information for the screening and early diagnosis of CRC. OBJECTIVES: The objective of our study was to determine whether fecal microRNAs (miR-29a, miR-145, miR-223, miR-224) could be used as biomarkers for the screening and early diagnosis of colorectal cancer. METHODS: We carried out a retrospective analysis of the miRNAs in fecal samples from 80 CRC patients and 51 normal controls. The levels of 4 miRNAs (miR-29a, miR-145, miR-223, and miR-224) were quantitated using the SYBR Green miScript PCR system and 2-Ct method. RESULTS: Our data indicated that the expression levels of miR-29a (p < 0.001), miR-223 (p < 0.001) and miR-224 (p < 0.001) are significantly lower in feces from CRC patients than these from normal volunteers, whereas their miR-145 levels are not significantly different (p = 0.59). Interestingly, the level of miR-29a (p < 0.001) in feces from individuals with rectum cancer is also significantly higher than that from patients with colon cancer. CONCLUSION: There are reduced expression of miR-29a, miR-223, and miR-224 in the feces from the CRC patients, which could be an informative biomarker for screening and early diagnosis of CRC. © 2016 - IOS Press and the authors. All rights reserved.


Huang Y.,Shanghai JiaoTong University | Huang Y.,Shanghai Colorectal Cancer Research Center | Wang G.,Shanghai JiaoTong University | Wang G.,Shanghai Colorectal Cancer Research Center | And 8 more authors.
Clinical Epigenetics | Year: 2016

5-Hydroxymethylcytosine (5hmC) is lost in multiple human cancers, including colorectal cancer (CRC). Decreased ten-eleven translocation 1 (TET1) messenger RNA (mRNA), but not other two TET family members, has been observed in the colorectal cancer and is crucial for colorectal cancer initiation. Here, we show that nuclear localization of TET2 was lost in a significant portion of CRC tissues, in association with metastasis. In CRC cells, nuclear expression of TET2 were absent but not TET3. Nuclear export inhibitor can increase the 5hmC level in CRC cells, probably through regulating TET2. Our results indicate a new mechanism of TET2 dysregulation in colorectal cancer. © 2016, Huang et al.


Wang G.,Shanghai JiaoTong University | Wang G.,Shanghai Colorectal Cancer Research Center | Shen W.,Shanghai JiaoTong University | Shen W.,Shanghai Colorectal Cancer Research Center | And 8 more authors.
Cancer Biomarkers | Year: 2016

BACKGROUND: Our previous study found ANLN was over-expressed in colorectal cancer(CRC), however the role of ANLN in CRC remained unknown. OBJECTIVE: To investigate the relationship of ANLN expression in CRC with clinical features and to determinate the prognostic significance of ANLN expression in CRC. METHODS: The ANLN expression in CRC tissue and adjacent normal colorectal mucosa were measured, the relationship between ANLN expression and clinical features as well as overall survival were analyzed. RESULTS: ANLN was overexpressed in CRC. ANLN expression was associated with tumor invasion and enlarged tumor size. Furthermore, Kaplan-Meier survival analysis revealed that higher expression of ANLN was associated with poorer overall survival. Multi-variate analysis suggested that higher expression of ANLN, preoperative CEA level and distant metastasis were independent prognostic factor in patients with CRC CONCLUSIONS: ANLN expression is elevated in CRC and has a strong potential to act as a biomarker for the prognosis of CRC. © 2016 - IOS Press and the authors.

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