Dataset Information

ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer.

ABSTRACT:

Background

Establishment of cohesion 1 homolog 2 (ESCO2) plays important roles in the regulation of cohesion and genomic stability and has been implicated in human cancers. Yet, its clinical significance and biological function in colorectal cancer (CRC) are unknown.

Methods

The expression of ESCO2 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of ESCO2 in the tumor metastasis of CRC and the related mechanisms were investigated using in vitro and in vivo models.

Results

In this study, we show that low expression of ESCO2 in CRC was closely correlated with lymphatic and distant metastasis. Patients with low ESCO2 expression experienced shorter overall survival and disease-free survival in two independent cohorts containing a total of 587 CRC cases. ESCO2 overexpression suppressed, whereas ESCO2 knockdown promoted cell migration in vitro and tumor metastasis in vivo via modulation of epithelial-mesenchymal transition (EMT) process. Mechanistically, ESCO2 inhibited the transcriptional activity of MMP2 promoter to downregulate its expression. Reexpression of MMP2 partially attenuated the ESCO2-mediated malignant phenotypes.

Conclusion

Collectively, our data suggest that ESCO2 serves as a potential prognostic factor and exerts antimetastatic activity in CRC.

SUBMITTER: Guo XB

PROVIDER: S-EPMC6257866 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer.

Guo Xiong-Bo XB Huang Bin B Pan Ying-Hua YH Su Shu-Guang SG Li Yan Y

Cancer management and research 20181122

<h4>Background</h4>Establishment of cohesion 1 homolog 2 (ESCO2) plays important roles in the regulation of cohesion and genomic stability and has been implicated in human cancers. Yet, its clinical significance and biological function in colorectal cancer (CRC) are unknown.<h4>Methods</h4>The expression of ESCO2 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of ESCO2 in the tumor metastasis of CRC and the related mechanisms were investigated using i ...[more]

PMID: 30538563

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Project description:Cancer cells use glucose and glutamine as the major sources of energy and precursor intermediates, and enhanced glycolysis and glutamimolysis are the major hallmarks of metabolic reprogramming in cancer. Oncogene activation and tumor suppressor gene inactivation alter multiple intracellular signaling pathways that affect glycolysis and glutaminolysis. N-Myc downstream regulated gene 2 (NDRG2) is a tumor suppressor gene inhibiting cancer growth, metastasis and invasion. However, the role and molecular mechanism of NDRG2 in cancer metabolism remains unclear. In this study, we discovered the role of the tumor suppressor gene NDRG2 in aerobic glycolysis and glutaminolysis of cancer cells. NDRG2 inhibited glucose consumption and lactate production, glutamine consumption and glutamate production in colorectal cancer cells. Analysis of glucose transporters and the catalytic enzymes involved in glycolysis revealed that glucose transporter 1 (GLUT1), hexokinase 2 (HK2), pyruvate kinase M2 isoform (PKM2) and lactate dehydrogenase A (LDHA) was significantly suppressed by NDRG2. Analysis of glutamine transporter and the catalytic enzymes involved in glutaminolysis revealed that glutamine transporter ASC amino-acid transporter 2 (ASCT2) and glutaminase 1 (GLS1) was also significantly suppressed by NDRG2. Transcription factor c-Myc mediated inhibition of glycolysis and glutaminolysis by NDRG2. More importantly, NDRG2 inhibited the expression of c-Myc by suppressing the expression of β-catenin, which can transcriptionally activate C-MYC gene in nucleus. In addition, the growth and proliferation of colorectal cancer cells were suppressed significantly by NDRG2 through inhibition of glycolysis and glutaminolysis. Taken together, these findings indicate that NDRG2 functions as an essential regulator in glycolysis and glutaminolysis via repression of c-Myc, and acts as a suppressor of carcinogenesis through coordinately targeting glucose and glutamine transporter, multiple catalytic enzymes involved in glycolysis and glutaminolysis, which fuels the bioenergy and biomaterials needed for cancer proliferation and progress.

Dataset Information

ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer.

Background

Methods

Results

Conclusion

Publications

ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer.

Similar Datasets

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