Loss of E-Cadherin Expression Is Associated with a Poor Prognosis in Stage III Colorectal Cancer

Yun, Jong Min; Kim, Seok-Hyung; Hong, Hye Kyung; Yun, Seong Hyeon; Kim, Hee Cheol; Chun, Ho-Kyung; Cho, Yong Beom; Lee, Woo Yong

doi:10.1159/000360794

Cited by 53 publications

(40 citation statements)

References 18 publications

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“…In CRCs, PAICS is involved in regulating the EMT, which is involved in regulation of cancer cell invasion and metastasis [44]. In CRCs, the loss of E-cadherin and gain of vimentin are implicated in cancer progression, and metastasis and are associated with a poor prognosis [45]. A previous study showed that the histone methyltransferase, EZH2, mediates transcriptional silencing of E-cadherin by trimethylation of H3 lysine 27 [46].…”

Section: Discussionmentioning

confidence: 99%

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer

Agarwal

Chakravarthi

Behring

et al. 2020

Cancers

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The identification of colorectal cancer (CRC) molecular targets is needed for the development of drugs that improve patient survival. We investigated the functional role of phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), a de novo purine biosynthetic enzyme involved in DNA synthesis, in CRC progression and metastasis by using cell and animal models. Its clinical utility was assessed in human CRC samples. The expression of PAICS was regulated by miR-128 and transcriptionally activated by Myc in CRC cells. Increased expression of PAICS was involved in proliferation, migration, growth, and invasion of CRC cells irrespective of the p53 and microsatellite status. In mice, the depletion of PAICS in CRC cells led to reduced tumor growth and metastatic cell dissemination to the liver, lungs, and bone. Positron emission tomography imaging showed significantly reduced metastatic lesions in stable PAICS knockdown CRC cells. In cells with PAICS knockdown, there was upregulation of the epithelial mesenchymal transition marker, E-cadherin, and bromodomain inhibitor, JQ1, can target its increased expression by blocking Myc. PAICS was overexpressed in 70% of CRCs, and was associated with poor 5-year survival independent of the pathologic stage, patient’s race, gender, and age. Overall, the findings point to the usefulness of PAICS targeting in the treatment of aggressive colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer

Agarwal

Chakravarthi

Behring

et al. 2020

Cancers

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“…invasion. E-cadherin loss is an integral step in the epithelial-mesenchymal transition (EMT), that is associated with tumor progression, invasion and metastasis in CRC (Heerboth et al 2015;Yun et al 2014). Conversely, increased E-cadherin expression has been shown to decrease ERK1/2 phosphorylation, suggesting a suppressor role in the Kras oncogenic pathway (Satow et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats

Caetano

Tablas

Pereira

et al. 2018

Toxicology and Applied Pharmacology

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Capsaicin (8-Methyl-N-vanillyl-(trans)-6-nonenamide) is the major pungent ingredient found in chili peppers consumed worldwide. Most reports on capsaicin potential carcinogenicity have yielded inconsistent findings. Some studies have shown that capsaicin exerts anti-proliferative and pro-apoptotic effects on different cancer cell lines, while others have reported an association between capsaicin at high doses with mutagenicity and carcinogenicity. Thus, this study aimed at assessing the effects of capsaicin administration on 1,2-dimethyl-hydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Our results show that capsaicin administration, before and during carcinogen exposure, modified DMH-induced cytotoxicity and genotoxicity, promoting anti-proliferative and pro-apoptotic responses through the expression of the genes involved in apoptosis, cell cycle suppression and cell/tissue differentiation. Furthermore, capsaicin reduced aberrant crypt foci (ACF) number and multiplicity, although there were no differences in tumor incidence and multiplicity among the groups. Taken together, the results suggest that capsaicin may have a preventive effect against DMH-induced colorectal carcinogenesis.

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“…22 Furthermore, intermediate filaments are shown to switch from cytokeratin to vimentin during EMT and increased vimentin levels are also a consistent marker during various EMT events. 23 In recent years, some of the metastatic actions of WAVE3 could be explained by its role in epithelial mesenchymal transition. Here, we showed that upregulating WAVE3 in SGC-7901 cells by pcDNA3.1-WAVE3 led to reduced expression of E-cadherin, and increased expression of vimentin.…”

Section: Discussionmentioning

confidence: 99%

WAVE3 promotes epithelial–mesenchymal transition of gastric cancer through upregulation of Snail

et al. 2014

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WAVE3, an actin cytoskeleton remodeling protein overexpressed in many kinds of cancers, has been associated with a lot of metastatic diseases. However, the role and mechanisms of the high expression of WAVE3 in human gastric cancer has not been fully elucidated. Here we demonstrated that WAVE3 was expressed in all six kinds of gastric-cancer cell lines: BGC-823, SGC-7901, AGS, MGC803, MKN28 and MKN45. Furthermore, a correlation was found between aggressiveness of these cell lines and expression of WAVE3. Next, we investigated the role of WAVE3 in SGC-7901 cells and found that upregulating WAVE3 could promote the migration, invasion and proliferation of SGC-7901 cells in vitro. It has been reported that WAVE3 could induce cancer invasion and metastasis by participating epithelial-mesenchymal transition (EMT). However, the mechanisms are not entirely clear. In this study we showed that elevated WAVE3 levels could induce EMT in SGC-7901 cells by dampening the expression of E-cadherin while increasing the expression of vimentin. Elevated WAVE3 levels could also improve the expression of transcription factor Snail. In addition, downregulating Snail could particularly reduce EMT and the metastasis, invasion and proliferation activity in SGC-7901 cells elevated by overexpression of WAVE3. Taken together, we demonstrated that WAVE3 promoted gastric-cancer-cells migration and invasion by taking part in EMT via upregulation of Snail. WAVE3 could be a useful target for gastric-cancer prevention and therapy.

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Loss of E-Cadherin Expression Is Associated with a Poor Prognosis in Stage III Colorectal Cancer

Cited by 53 publications

References 18 publications

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats

WAVE3 promotes epithelial–mesenchymal transition of gastric cancer through upregulation of Snail

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