Cellular density‐dependent increases in <scp>HIF</scp>‐1α compete with c‐Myc to down‐regulate human <scp>EP</scp>4 receptor promoter activity through Sp‐1‐binding region

Seira, Naofumi; Yamagata, Kunio; Fukushima, Keijo; Araki, Yoshinori; Kurata, Nori; Yanagisawa, Naoki; Mashimo, Masato; Nakamura, Hiroyuki; Regan, John W.; Murayama, Toshihiko; Fujino, Hiromichi

doi:10.1002/prp2.441

Cited by 7 publications

(3 citation statements)

References 34 publications

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“…It was shown that HIF1α displaces MYC binding from the p21 promoter and upregulates the expression of p21 (Koshiji et al, 2004). HIF1α also competes against MYC for binding to SP1, a known coactivator of MYC, at the promoters of MYC target genes, such as MSH2, MSH6, and NBS1, which encode DNA repair proteins (Koshiji et al, 2005;To et al, 2006), and the recently reported E−type prostanoid (EP4) receptors (Seira et al, 2018). Third, several studies showed that HIF promotes proteasomal degradation of MYC under chronic hypoxia condition (Zhang et al, 2007;Wong et al, 2013).…”

Section: The Regulation Of Myc By Hifmentioning

confidence: 99%

Molecular Crosstalk Between MYC and HIF in Cancer

Li¹,

Sun²,

Qian

et al. 2020

Front. Cell Dev. Biol.

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The transcription factor c-MYC (MYC thereafter) is a global regulator of gene expression. It is overexpressed or deregulated in human cancers of diverse origins and plays a key role in the development of cancers. Hypoxia-inducible factors (HIFs), a central regulator for cells to adapt to low cellular oxygen levels, is also often overexpressed and activated in many human cancers. HIF mediates the primary transcriptional response of a wide range of genes in response to hypoxia. Earlier studies focused on the inhibition of MYC by HIF during hypoxia, when MYC is expressed at physiological level, to help cells survive under low oxygen conditions. Emerging evidence suggests that MYC and HIF also cooperate to promote cancer cell growth and progression. This review will summarize the current understanding of the complex molecular interplay between MYC and HIF.

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Section: The Regulation Of Myc By Hifmentioning

confidence: 99%

Molecular Crosstalk Between MYC and HIF in Cancer

Li¹,

Sun²,

Qian

et al. 2020

Front. Cell Dev. Biol.

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“…Kambe et al reported that specificity protein 1 (Sp-1) binds to the region −197 to −160 of the EP4 promoter to promote its expression ( 30 ). EP4 expression is enhanced by c-Myc, which binds to Sp-1 under low cellular density conditions, but is downregulated under high cellular density conditions via HIF-1α, which may prevent c-Myc and Sp-1 from DNA-binding in normal colorectal epithelial cells ( 31 ). Oh et al found that human papillomavirus E5 protein induces EP4 expression in cAMP response element (CRE)-dependent pathway in cervical cancer cells, which is inhibited by an EP4 antagonist, inhibitor of cAMP-dependent protein kinase or phosphatidylinositol 3-kinase, and CRE decoy ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

TFF3 promotes clonogenic survival of colorectal cancer cells through upregulation of EP4 via activation of STAT3

Yang¹,

Fu²,

Tian³

et al. 2023

Transl Cancer Res

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Background While growing evidence indicates the importance of TFF3 in cancer, the molecular mechanism of its action in cancer remains largely unknown. Clonogenic survival is a key ability for tumor cells, which is interpreted as a trait of cancer cells with tumor-initiating capabilities. We investigated the effect and the underlying mechanisms of TFF3 on the clonogenic survival of colorectal cancer (CRC) cells. Methods Expression of TFF3 in CRC tissues and matched paracancerous tissues was determined by western blotting. Colony formation assays were performed to evaluate the clonogenic survival ability of CRC cells. PTGER4 mRNA expression was detected by quantitative polymerase chain reaction. PTGER4 promoter activity was determined by luciferase reporter assay. STAT3 nuclear localization was investigated using immunofluorescence staining. Expression of TFF3 and EP4 in CRC tissues was determined by immunohistochemistry. Results TFF3 knockout led to decreased clonogenic survival of CRC cells, while overexpression of TFF3 resulted in the opposite effect. EP4 was found to be upregulated by TFF3 at both the mRNA and protein level. Moreover, EP4 antagonist abrogated TFF3-mediated clonogenic survival of CRC cells. PGE2 and EP4 agonist could restore the effect of TFF3 knockout on the clonogenic survival of CRC cells. Furthermore, TFF3 promoted STAT3 activation and nuclear localization. Activated STAT3 bound to PTGER4 promoter, the gene encoding for EP4, and facilitated PTGER4 transcription. Conclusions TFF3 promotes clonogenic survival of CRC cells via upregulating EP4 expression.

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“…For instance, HIF1A displaces MYC binding from the promoter of cyclin-dependent kinase inhibitor 1A (CDKN1A, p21cip1) and upregulates the expression of p21 (CDKN1A) in human HCT116 colorectal carcinoma cell line [106]. HIF1A also competes against MYC for binding to SP1, a coactivator of MYC, at the promoters of MYC target genes such as MutS homolog 2 (MSH2), MSH6, and nibirin, which encode DNA repair proteins, in human HCT116 colorectal carcinoma cell line [107,108] and the E-type prostanoid receptor in human HCA-7 colon cancer cell line [109]. Third, several studies have shown that HIF-1A promotes proteasomal degradation of MYC under chronic hypoxia conditions [104,[110][111][112].…”

Section: Effects Of Hif-1 Compared To the Effects Of Sp1 On Myc Gene ...mentioning

confidence: 99%

Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development

Kimura,

Jackson,

Huang

2023

CIMB

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Specificity protein 1 (SP1), hypoxia-inducible factor 1 (HIF-1), and MYC are important transcription factors (TFs). SP1, a constitutively expressed housekeeping gene, regulates diverse yet distinct biological activities; MYC is a master regulator of all key cellular activities including cell metabolism and proliferation; and HIF-1, whose protein level is rapidly increased when the local tissue oxygen concentration decreases, functions as a mediator of hypoxic signals. Systems analyses of the regulatory networks in cancer have shown that SP1, HIF-1, and MYC belong to a group of TFs that function as master regulators of cancer. Therefore, the contributions of these TFs are crucial to the development of cancer. SP1, HIF-1, and MYC are often overexpressed in tumors, which indicates the importance of their roles in the development of cancer. Thus, proper manipulation of SP1, HIF-1, and MYC by appropriate agents could have a strong negative impact on cancer development. Under these circumstances, these TFs have naturally become major targets for anticancer drug development. Accordingly, there are currently many SP1 or HIF-1 inhibitors available; however, designing efficient MYC inhibitors has been extremely difficult. Studies have shown that SP1, HIF-1, and MYC modulate the expression of each other and collaborate to regulate the expression of numerous genes. In this review, we provide an overview of the interactions and collaborations of SP1, HIF1A, and MYC in the regulation of various cancer-related genes, and their potential implications in the development of anticancer therapy.

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Cellular density‐dependent increases in HIF‐1α compete with c‐Myc to down‐regulate human EP4 receptor promoter activity through Sp‐1‐binding region

Cited by 7 publications

References 34 publications

Molecular Crosstalk Between MYC and HIF in Cancer

Molecular Crosstalk Between MYC and HIF in Cancer

TFF3 promotes clonogenic survival of colorectal cancer cells through upregulation of EP4 via activation of STAT3

Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development

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