TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling

Dai, Yaozhang; Duan, Hong; Duan, Chaojun; Zhu, Hong; Zhou, Rongrong; Pei, Haiping; Shen, Liangfang

doi:10.2147/ott.s118151

Cited by 31 publications

(39 citation statements)

References 25 publications

(30 reference statements)

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“…The study carried out by Tan et al reported that enforced expression of TCF21 could reduce the proliferation and migration of HCC cells and enhance apoptosis in vitro [15]. Dai et al revealed that TCF21 might inhibit tumor progression in colorectal cancer through suppressing PI3K/AKT signaling pathway [24]. Besides, two published studies have demonstrated that the down-regulation of TCF21 could inactivate metastasis suppressor KISS1, thus leading to cancer metastasis [25,26].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Expression tendency and prognostic value of TCF21 in hepatocellular carcinoma

Yang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Transcription factor 21 (TCF21) is identified as a tumor suppressor in a variety of human tumors. The purpose of the study was to examine its expression tendency and prognostic value in hepatocellular carcinoma (HCC). Methods: Relative expression of TCF21 mRNA in tissue samples from HCC patients and healthy volunteers were detected through quantitative real-time polymerase chain reaction (qRT-PCR) while its protein level was examined via immunohistochemistry analysis. Chi-square test was adopted to assess the association of TCF21 expression with the clinicopathological characteristic of the patients. Then Kaplan-Meier analysis was employed to analyze the function of TCF21 expression on overall survival among HCC patients. Results: Both the mRNA and protein levels of TCF21 were significantly reduced in HCC tissue samples compared with healthy controls (p < .05). Also, its expression was obviously affected by the classification of tissue pathology, metastasis, T stage, N stage and pathological grading. According to Kaplan-Meier analysis, patients with higher expression of TCF21 experienced dramatically longer overall survival time than those with lower expression (log rank test, p < .001). Conclusions: TCF21 expression was decreased in HCC patients and it could act as a prognostic marker.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Expression tendency and prognostic value of TCF21 in hepatocellular carcinoma

Yang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Low TCF21 expression has been shown to be related to high-grade or invasive–aggressive cancers with lymph node or distant metastases indicating recurrence and with an inferior prognosis. 24 , 26 TCF21 may thus serve as an excellent diagnostic or prognostic biomarker predicting poor outcome, as demonstrated in gastric cancer, 25 melanoma, 29 colorectal cancer, 39 and lung cancer cases. 38 , 40 Aberrant methylation of TCF21 can be detected not only in solid cancer tissues but also in sputum and urine samples from cancer patients.…”

Section: Regulation Of Tcf21 Expressionmentioning

confidence: 99%

“…A recent study confirmed that upregulation of TCF21 significantly increased the expression of KISS1 and decreased the expression of phosphatidylinositol 3-hydroxy kinase (PI3K) and phosphorylated AKT, indicating inactivation of PI3K/AKT signaling. 39 In addition, overexpression of TCF21 also inhibited the expression of matrix metalloproteinase (MMP)-2 and MMP-9, which are involved in cancer cell invasion and metastasis. 39 Similarly, Wei et al 28 demonstrated that TCF21 inhibited MMP-2 and MMP-10 and decreased ovarian cancer cell invasion.…”

Section: Tumor Suppressive Signatures Of Tcf21mentioning

confidence: 99%

“… 39 In addition, overexpression of TCF21 also inhibited the expression of matrix metalloproteinase (MMP)-2 and MMP-9, which are involved in cancer cell invasion and metastasis. 39 Similarly, Wei et al 28 demonstrated that TCF21 inhibited MMP-2 and MMP-10 and decreased ovarian cancer cell invasion. In addition, Arab et al 29 reported that TCF21 was regulated epigenetically and had potential antimetastatic properties by directly activating the known metastasis suppressor KISS1 on chromosome 1q32 in melanoma.…”

Section: Tumor Suppressive Signatures Of Tcf21mentioning

confidence: 99%

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Multiple biological functions of transcription factor 21 in the development of various cancers

Jiang¹,

Yang²

2018

OTT

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Transcription factor 21 (TCF21) is a basic helix–loop–helix transcription factor that binds to DNA and regulates cell differentiation and cell fate specification through mesenchymal–epithelial transition during development. The TCF21 gene is epigenetically inactivated in many types of human cancers and exerts a wide variety of functions, including the regulation of epithelial–mesenchymal transition, invasion, metastasis, cell cycle, and autophagy. This review focuses on research progress in relation to the roles of TCF21 in tumor development. We systematically consider multiple pathological functions of TCF21 in various cancers, revealing the molecular bases of its diverse biological roles and providing new directions for future research.

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“…Therefore, increase in CDH1 expression might be a possible reason for decreased migration of TCF21 ‐expressing 786‐O cells in the current study, through alternative downstream transcriptional pathways, because we did not detect changes in the extracellular epitope for CDH1 (Canel et al ., ; Onder et al ., ). Furthermore, our results that overexpression of TCF21 inhibits migration are in accordance with in vitro studies in colorectal cancer cell lines (Dai et al ., , ) as well as siRNA suppression of endogenous TCF21 in renal progenitor cells which increased migration (Plotkin and Mudunuri, ). Although re‐expression of TCF21 in melanoma cells and Caki‐1 ccRCC cells has been described to activate expression of the metastatic suppressor KISS1 (Arab et al ., ; Zhang et al ., ), in the current study KISS1 expression does not seem to be involved in the suppressed migration of 786‐O cells transfected with TCF21 .…”

Section: Discussionmentioning

confidence: 99%

TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration

et al. 2017

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We recently identified hypermethylation at the gene promoter of transcription factor 21 (TCF21) in clear cell sarcoma of the kidney (CCSK), a rare pediatric renal tumor. TCF21 is a transcription factor involved in tubular epithelial development of the kidney and is a candidate tumor suppressor. As there are no in vitro models of CCSK, we employed a well‐established clear cell renal cell carcinoma (ccRCC) cell line, 786‐O, which also manifests high methylation at the TCF21 promoter, with consequent low TCF21 expression. The tumor suppressor function of TCF21 has not been functionally addressed in ccRCC cells; we aimed to explore the functional potential of TCF21 expression in ccRCC cells in vitro. 786‐O clones stably transfected with either pBABE‐TCF21‐HA construct or pBABE vector alone were functionally analyzed. We found that ectopic expression of TCF21 in 786‐O cells results in a trend toward decreased cell proliferation (not significant) and significantly decreased migration compared with mock‐transfected 786‐O cells. Although the number of colonies established in colony formation assays was not different between 786‐O clones, colony size was significantly reduced in 786‐O cells expressing TCF21. To investigate whether the changes in migration were due to epithelial‐to‐mesenchymal transition changes, we interrogated the expression of selected epithelial and mesenchymal markers. Although we observed upregulation of mRNA and protein levels of epithelial marker E‐cadherin in clones overexpressing TCF21, this did not result in surface expression of E‐cadherin as measured by fluorescence‐activated cell sorting and immunofluorescence. Furthermore, mRNA expression of the mesenchymal markers vimentin (VIM) and SNAI1 was not significantly decreased in TCF21‐expressing 786‐O cells, while protein levels of VIM were markedly decreased. We conclude that re‐expression of TCF21 in renal cancer cells that have silenced their endogenous TCF21 locus through hypermethylation results in reduced clonogenic proliferation, reduced migration, and reduced mesenchymal‐like characteristics, suggesting a tumor suppressor function for transcription factor 21.

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TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling

Cited by 31 publications

References 25 publications

RETRACTED ARTICLE: Expression tendency and prognostic value of TCF21 in hepatocellular carcinoma

RETRACTED ARTICLE: Expression tendency and prognostic value of TCF21 in hepatocellular carcinoma

Multiple biological functions of transcription factor 21 in the development of various cancers

TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration

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