Myocyte enhancer factor 2D promotes colorectal cancer angiogenesis downstream of hypoxia-inducible factor 1α

Xiang, Junyu; Sun, Hui; Su, Li; Liu, Limei; Shan, Juanjuan; Shen, Junjie; Yang, Zhi; Chen, Jun; Zhong, Xing; Ávila, Matías A.; Xi, Yan; Liu, Chungang; Qian, Cheng

doi:10.1016/j.canlet.2017.04.037

Cited by 25 publications

(17 citation statements)

References 42 publications

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“…Hypoxiainducible factor 1α (HIF-1α) is a heterodimeric transcription factor that is activated during hypoxic oxygen levels and regulates the expression of several genes [5][6][7][8] involved in cell metastasis and angiogenesis. Moreover, overexpression of HIF1a has been associated with a poor prognostic outcome in multiple types of cancer, including poor prognostic factors for CRC [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues. Methods: The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis. Using chromatin-immunoprecipitation (ChIP), quantitative real-time PCR, Western blot, and transwell assay, the functional role and underlying mechanism of SRGN in CRC metastasis were elucidated. Thus, this study provides evidence of a critical role of SRGN in metastatic progression of CRC. Results: Our results indicated that SRGN overexpression was significantly associated with poor prognosis in CRC specimens. SRGN overexpression promoted CRC cell migration and invasion in vitro; however, SRGN depletion exhibited contrasting effects. Mechanistic investigations revealed that HIF-1α regulated SRGN transcription via physically binding to a hypoxia response element in its promoter region. Conclusions: In conclusion, we demonstrated that dysregulated HIF-1α/SRGN signaling promotes CRC progression and metastasis. SRGN may serve as a potential candidate therapeutic target for metastatic CRC.

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Section: Introductionmentioning

confidence: 99%

SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

Yang

et al. 2018

Cell Physiol Biochem

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“…Furthermore, dysregulation of the MEF2 family has important implications in tumorigenesis ( Di Giorgio et al, 2018 ). In colorectal cancer, MEF2D is a target gene of HIF1α, and MEF2D enhances transcriptional upregulation of proangiogenic cytokines ( Xiang et al, 2017 ).…”

Section: G9a- and Glp-dependent Non-histone Protein Methylationmentioning

confidence: 99%

Hypoxia-Inducible Lysine Methyltransferases: G9a and GLP Hypoxic Regulation, Non-histone Substrate Modification, and Pathological Relevance

et al. 2020

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Oxygen sensing is inherent among most animal lifeforms and is critical for organism survival. Oxygen sensing mechanisms collectively trigger cellular and physiological responses that enable adaption to a reduction in ideal oxygen levels. The major mechanism by which oxygen-responsive changes in the transcriptome occur are mediated through the hypoxia-inducible factor (HIF) pathway. Upon reduced oxygen conditions, HIF activates hypoxia-responsive gene expression programs. However, under normal oxygen conditions, the activity of HIF is regularly suppressed by cellular oxygen sensors; prolyl-4 and asparaginyl hydroxylases. Recently, these oxygen sensors have also been found to suppress the function of two lysine methyltransferases, G9a and G9a-like protein (GLP). In this manner, the methyltransferase activity of G9a and GLP are hypoxia-inducible and thus present a new avenue of low-oxygen signaling. Furthermore, G9a and GLP elicit lysine methylation on a wide variety of non-histone proteins, many of which are known to be regulated by hypoxia. In this article we aim to review the effects of oxygen on G9a and GLP function, non-histone methylation events inflicted by these methyltransferases, and the clinical relevance of these enzymes in cancer.

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“…The effect of HIF-1α on the angiogenic potential of small cell lung cancer (SCLC) significantly upregulated the expression of pro-angiogenic genes including VEGF-A, TNFA1P6, PDGFC, FN1, MMP 28 and MMP14 [83]. Myocyte enhancer factor 2D (MEF2D) has also been proven to play a central role in tumour angiogenesis [84]. MEF2D expression positively correlated with colorectal tumour angiogenesis, through the induction of pro-angiogenic factors including PDGF-BB, PDGF-C, PLGF, milk fat globule factor (MFG)-E8, and tumour necrosis factor superfamily member (TNFRSF).…”

Section: Angiogenesismentioning

confidence: 99%

Exploiting Current Understanding of Hypoxia Mediated Tumour Progression for Nanotherapeutic Development

Feng

Byrne

Jamal

et al. 2019

Cancers

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Hypoxia is one of the most common phenotypes of malignant tumours. Hypoxia leads to the increased activity of hypoxia-inducible factors (HIFs), which regulate the expression of genes controlling a raft of pro-tumour phenotypes. These include maintenance of the cancer stem cell compartment, epithelial-mesenchymal transition (EMT), angiogenesis, immunosuppression, and metabolic reprogramming. Hypoxia can also contribute to the tumour progression in a HIF-independent manner via the activation of a complex signalling network pathway, including JAK-STAT, RhoA/ROCK, NF-κB and PI3/AKT. Recent studies suggest that nanotherapeutics offer a unique opportunity to target the hypoxic microenvironment, enhancing the therapeutic window of conventional therapeutics. In this review, we summarise recent advances in understanding the impact of hypoxia on tumour progression, while outlining possible nanotherapeutic approaches for overcoming hypoxia-mediated resistance.

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Myocyte enhancer factor 2D promotes colorectal cancer angiogenesis downstream of hypoxia-inducible factor 1α

Cited by 25 publications

References 42 publications

SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

Hypoxia-Inducible Lysine Methyltransferases: G9a and GLP Hypoxic Regulation, Non-histone Substrate Modification, and Pathological Relevance

Exploiting Current Understanding of Hypoxia Mediated Tumour Progression for Nanotherapeutic Development

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