p63-Mediated activation of the β-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis

Lee, Kwang Bok; Ye, Shuai; Park, Man Hee; Park, Byung Hyun; Lee, Ju Seog; Kim, Soo Mi

doi:10.1016/j.canlet.2014.07.016

Cited by 35 publications

(28 citation statements)

References 29 publications

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“…When β-catenin phosphorylation was downregulated by PGE2 at Ser33, Ser37 and Thr41, the ubiquitin-dependent degradation was inhibited, and β-catenin accumulated in the cytoplasm forming a complex with the transcription factor, lymphoid enhancing factor-1/T-cell factor, which is subsequently transported into the cell nucleus (50). This transcription complex activates the expression of downstream target genes, including c-Jun, c-Fos, c-Myc (27), Snail (28), cyclin D1 (29) and survivin, resulting in abnormal cell proliferation and cell carcinogenesis. Our results show that the expression of c-Myc and Snail which is associated with hepatic carcinoma progression observed in previous studies (6,9) also induced an increase of the EP3 receptor agonist.…”

Section: +mentioning

confidence: 99%

“…β-catenin was accumulated in the nucleus induced by PGE2 in cholangiocarcinoma cells (26). The accumulation of β-catenin in the nucleus induced transcription of important downstream target genes, such as c-Myc and Snail (27,28). The protein and mRMA levels were determined after pcDNA-EP3-4 transtected CCLP1 cells treated with 5 µM sulprostone for the indicated time periods.…”

Section: Pge2-associated β-Catenin Induces the Upregulation Of Downstmentioning

confidence: 99%

“…The activation of β-catenin was also involved in various stages of hepatic carcinoma (21)(22)(23)(24) and cholangiocarcinoma (25,26). β-catenin leads to the activation of target genes such as c-Myc (27), Snail (28) and cyclin D1 (29). Although β-catenin has been regarded as a useful biomarker of cancer progression, the detailed mechanisms for its tumor-promoting function remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Prostaglandin E2 promotes human cholangiocarcinoma cell proliferation, migration and invasion through the upregulation of β-catenin expression via EP3-4 receptor

Feng

Zhang

et al. 2015

Oncology Reports

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Abstract. Prostaglandin E2 (PGE2) is involved in cholangiocarcinoma cell proliferation, migration and invasion through E prostanoid receptors, including EP1, EP2 and EP4. However, the functions and the mechanisms of those splice variants of EP3 receptors in promoting liver cancer cell growth and invasion remain to be elucidated. In our previous studies, four isoforms of EP3 receptors, EP3-4, EP3-5, EP3-6 and EP3-7 receptors, were detected in CCLP1 and HuCCT1 cells. However, the functions of these receptors in these cells have yet to be determined. It was reported that β-catenin is closely correlated with malignancy, including cholangiocarcinoma. The present study was designed to examine the effects of 4-7 isoforms of EP3 in promoting cholangiocarcinoma progression and the mechanisms by which PGE2 increases β-catenin protein via EP3 receptors. The results showed that PGE2 promotes cholangiocarcinoma progression via the upregulation of β-catenin protein, and the EP3-4 receptor pathway is mainly responsible for this regulation. These findings reveal that PGE2 upregulated the cholangiocarcinoma cell β-catenin protein through the EP3-4R/Src/EGFR/PI3K/AKT/GSK-3β pathway. The present study identified the functions of EP3 and the mechanisms by which PGE2 regulates β-catenin expression and promoted cholangiocarcinoma cell growth and invasion.

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Section: +mentioning

confidence: 99%

Section: Pge2-associated β-Catenin Induces the Upregulation Of Downstmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prostaglandin E2 promotes human cholangiocarcinoma cell proliferation, migration and invasion through the upregulation of β-catenin expression via EP3-4 receptor

Feng

Zhang

et al. 2015

Oncology Reports

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“…β-catenin is considered to be a key signaling protein in the regulation of cell proliferation (19)(20)(21). HepG2 cells were incubated in a sealed hypoxia chamber for 24 h, which resulted in significantly higher levels of β-catenin compared with cells in normoxic conditions ( Fig.…”

Section: E Resultsmentioning

confidence: 99%

“…2B). As C-Myc is a key downstream protein in β-catenin-mediated cell proliferation (19)(20)(21), the effects of C-Myc shRNA transfection were investigated in HepG2 cells. C-Myc shRNA decreased C-Myc and PCNA expression with no effect on the expression of HIF-2α and β-catenin (Fig.…”

Section: E Resultsmentioning

confidence: 99%

Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma

Liu

Dong

et al. 2015

Oncology Letters

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Abstract. Sorafenib is a type of multikinase inhibitor that exhibits antiangiogenic and antiproliferative effects; in addition, sorafenib is a unique first-line drug recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, the effectiveness of HCC treatment remains poor due to acquired drug resistance. It has been suggested that hypoxia, induced as a results of the antiangiogenic effects of sustained sorafenib treatment, may be an important factor in sorafenib resistance. The transcription factor hypoxia-inducible factor (HIF)-2α has been reported to be associated with cell proliferation under hypoxic conditions; therefore, it was hypothesized that hypoxia may enhance tumor cell proliferation via this mechanism. The present study aimed to evaluate whether the knock-down of HIF-2α was able to enhance the therapeutic efficacy of sorafenib in order to effectively treat HCC. The results demonstrated that hypoxia protected HCC cells against sorafenib; however, short hairpin RNA-HIF-2α transfection in combination with sorafenib treatment exhibited a significantly synergistic effect against HCC cell proliferation. In addition, HCC cells acquired increased β-catenin/C-Myc expression, which enhanced proliferation under hypoxic conditions; however, targeted knock-down of HIF-2α or C-Myc markedly decreased cell proliferation in HCC cells. In conclusion, the results of the present study indicated that the targeted knock-down of HIF-2α in combination with sorafenib may be a promising strategy for the treatment of HCC.

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ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment

Gatti

Fernanda

Annicchiarico-Petruzzelli

et al. 2019

Molecular Oncology

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Squamous cell carcinoma ( SCC ) is a treatment‐refractory tumour which arises from the epithelium of diverse anatomical sites such as oesophagus, head and neck, lung and skin. Accumulating evidence has revealed a number of genomic, clinical and molecular features commonly observed in SCC of distinct origins. Some of these genetic events culminate in fostering the activity of ΔNp63, a potent oncogene which exerts its pro‐tumourigenic effects by regulating specific transcriptional programmes to sustain malignant cell proliferation and survival. In this review, we will describe the genetic and epigenetic determinants underlying ΔNp63 oncogenic activities in SCC , and discuss some relevant transcriptional effectors of ΔNp63, emphasizing their impact in modulating the crosstalk between tumour cells and tumour microenvironment ( TME ).

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p63-Mediated activation of the β-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis

Cited by 35 publications

References 29 publications

Prostaglandin E2 promotes human cholangiocarcinoma cell proliferation, migration and invasion through the upregulation of β-catenin expression via EP3-4 receptor

Prostaglandin E2 promotes human cholangiocarcinoma cell proliferation, migration and invasion through the upregulation of β-catenin expression via EP3-4 receptor

Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma

ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment

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