TGIF transcription factors repress acetyl CoA metabolic gene expression and promote intestinal tumor growth

Shah, Anant; Melhuish, Tiffany A.; Fox, Todd E.; Frierson, Henry F.; Wotton, David

doi:10.1101/gad.320127.118

Cited by 19 publications

(15 citation statements)

References 69 publications

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“…In harmony with an oncogenic role of TGIF in breast cancer, silencing of TGIF was found to suppress the migration, invasion and metastasis of the human breast cancer cells in both in vitro and in vivo experiments ( Wang et al, 2018c ). TGIF1 has also been found to be significantly upregulated in some colorectal cancers and to promote adenoma growth in the context of mutant Apc ( Shah et al, 2019 ). Overexpression of TGIF1 markedly promoted the proliferation of colorectal cancer cells through the activation of Wnt/β-catenin signaling ( Wang et al, 2017c ).…”

Section: Examples Of Genes With Strong Signatures Of Positive And/or mentioning

confidence: 99%

“…TGIF1 has also been found to be significantly upregulated in some colorectal cancers and to promote adenoma growth in the context of mutant Apc ( Shah et al, 2019 ). Overexpression of TGIF1 markedly promoted the proliferation of colorectal cancer cells through the activation of Wnt/β-catenin signaling ( Wang et al, 2017c ).…”

Section: Examples Of Genes With Strong Signatures Of Positive And/or mentioning

confidence: 99%

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Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

Bányai

Trexler

Kerekes

et al. 2021

eLife

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A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. We have re-examined the role of negative selection in tumor evolution through the analysis of the patterns of somatic mutations affecting the coding sequences of human genes. Our analyses have confirmed that tumor suppressor genes are positively selected for inactivating mutations, oncogenes, however, were found to display signals of both negative selection for inactivating mutations and positive selection for activating mutations. Significantly, we have identified numerous human genes that show signs of strong negative selection during tumor evolution, suggesting that their functional integrity is essential for the growth and survival of tumor cells.

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Section: Examples Of Genes With Strong Signatures Of Positive And/or mentioning

confidence: 99%

Section: Examples Of Genes With Strong Signatures Of Positive And/or mentioning

confidence: 99%

Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

Bányai

Trexler

Kerekes

et al. 2021

eLife

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“…Moreover, miR-296 is also indicative of metastasis and epithelial-mesenchymal transition of CRC [ 13 ]. Thymine-guanine-interacting factors (TGIFs) are up-regulated in mutant colon tumors which assist to reprogram the expression of metabolic genes [ 14 ]. TGIF1 is a transcriptional co-repressor which exerts as a tumor promoter of CRC exacerbation [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis

Liu

et al. 2020

J Exp Clin Cancer Res

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Background The mechanism of histone deacetylase 3 (HDAC3) in colorectal cancer (CRC) has already been discussed. However, the feedback loop of HDAC3/microRNA (miR)-296-3p and transforming growth factor β-induced factor 1 (TGIF1) in CRC has not been explained clearly. Thus, the mainstay of this study is to delve out the mechanism of this axis in CRC. Methods To demonstrate that HDAC3 regulates the miR-296-3p/TGIF1/TGFβ axis and is involved in CRC progression, a series of cell biological, molecular and biochemical approaches were conducted from the clinical research level, in vitro experiments and in vivo experiments. These methods included RT-qPCR, Western blot assay, cell transfection, MTT assay, EdU assay, flow cytometry, scratch test, Transwell assay, dual luciferase reporter gene assay, chromatin immunoprecipitation, nude mouse xenograft, H&E staining and TUNEL staining. Results Higher HDAC3 and TGIF1 and lower miR-296-3p expression levels were found in CRC tissues. HDAC3 was negatively connected with miR-296-3p while positively correlated with TGIF1, and miR-296-3p was negatively connected with TGIF1. Depleted HDAC3 elevated miR-296-3p expression and reduced TGIF1 expression, decreased TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by miR-296-3p knockdown. Restored miR-296-3p suppressed TGIF1 and reduced TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by TGIF1 overexpression. Conclusion This study illustrates that down-regulation of HDAC3 or TGIF1 or up-regulation of miR-296-3p discourages CRC cell progression and slows down tumor growth, which guides towards a novel direction of CRC treatment.

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“…Previous studies have reported that TGIF1 plays a critical role in tumor initiation and progression, and its overexpression is associated with a poor prognosis of patients with colorectal ( 10 , 11 ), lung ( 12 ), gastric ( 22 ) and breast ( 13 , 23 ) cancer. The study by Wang et al demonstrated that TGIF1 was upregulated in colorectal cancer and functioned as an oncogene, promoting cancer cell proliferation and migration ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…It has been widely accepted that TGFB induced factor homeobox 1 (TGIF1), a member of the TGIF family, functions as a transcriptional repressor of TGF-β signaling and retinoid X receptor (RXR) signaling ( 7 , 8 ). Recent studies have demonstrated that TGIF is also involved in Wnt/β-catenin signaling ( 9 , 10 ) and regulates basic energy metabolism in cells ( 11 ). Consistent with the critical roles of TGIF1 in the regulation of important signaling pathways, TGIF1 has also been shown to be involved in tumorigenesis and tumor development, such as in lung ( 12 ), breast ( 13 ) and colorectal ( 14 ) cancer.…”

Section: Introductionmentioning

confidence: 99%

TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/β‑catenin and Akt/mTOR signaling pathways

Kong

Guan

et al. 2021

Int J Mol Med

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TGFB induced factor homeobox 1 (TGIF1), a transcriptional corepressor, has been reported to be involved in tumorigenesis and cancer development. However, the role of TGIF1 in the growth and metastasis of esophageal cancer is poorly studied. In the present study, it was found that TGIF1 was highly expressed in esophageal cancer tissues and cell lines. The silencing of TGIF1 by siRNA interference significantly inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process of KYSE-150 esophageal cancer cells, and promoted cell apoptosis. Correspondingly, the upregulation of TGIF1 significantly promoted the proliferation and metastatic potential of Eca-109 cells, and reduced apoptosis. Furthermore, the data indicated that the Wnt/β-catenin and Akt/mammalian target of rapamycin (mTOR) signaling pathways were inhibited by TGIF1 knockdown, and were promoted by the overexpression of TGIF1. It was also confirmed that TGIF1 knockdown reduced tumor growth, inhibited Wnt/β-catenin and Akt/mTOR pathway activation, and reversed the TGF-β1-mediated EMT process in a tumor xenograft model. Taken together, the data of the present study suggest that TGIF1 plays an oncogenic role in the progression of esophageal cancer. It may carry out this role by regulating the Wnt/β-catenin and Akt/mTOR signaling pathways.

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TGIF transcription factors repress acetyl CoA metabolic gene expression and promote intestinal tumor growth

Cited by 19 publications

References 69 publications

Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis

TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/β‑catenin and Akt/mTOR signaling pathways

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