Transcription Factors in Cancer Development and Therapy

Vishnoi, Kanchan; Viswakarma, Navin; Rana, Ajay; Rana, Basabi

doi:10.3390/cancers12082296

Cited by 86 publications

(53 citation statements)

References 259 publications

(248 reference statements)

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“…In cancers, erroneous activation allows β-catenin to leave the membrane and translocate to the nucleus. There β-catenin acts as a transcription co-factor and drives transcription of proteins that support the epithelial-mesenchymal transition, invasion, and metastasis 31 , 32 . We stained breast tumor tissues, to evaluate the distribution of the β-catenin protein.…”

Section: Resultsmentioning

confidence: 99%

Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer

et al. 2021

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Triple-negative breast cancer (TNBC) patients with upregulated Wnt/β-catenin signaling often have poor clinical prognoses. During pathological examinations of breast cancer sections stained for β-catenin, we made the serendipitous observation that relative to non-TNBC, specimens from TNBC patients have a greater abundance of nucleoli. There was a remarkable direct relationship between nuclear β-catenin and greater numbers of nucleoli in TNBC tissues. These surprising observations spurred our investigations to decipher the differential functional relevance of the nucleolus in TNBC versus non-TNBC cells. Comparative nucleolar proteomics revealed that the majority of the nucleolar proteins in TNBC cells were potential targets of β-catenin signaling. Next, we undertook an analysis of the nucleolar proteome in TNBC cells in response to β-catenin inhibition. This effort revealed that a vital component of pre-rRNA processing, LAS1 like ribosome biogenesis factor (LAS1L) was significantly decreased in the nucleoli of β-catenin inhibited TNBC cells. Here we demonstrate that LAS1L protein expression is significantly elevated in TNBC patients, and it functionally is important for mammary tumor growth in xenograft models and enables invasive attributes. Our observations highlight a novel function for β-catenin in orchestrating nucleolar activity in TNBCs.

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Section: Resultsmentioning

confidence: 99%

Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer

et al. 2021

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“…As we demonstrated in this study, β-catenin is normally localized on the cytomembranes of non-neoplastic epithelial cells in the colonic mucosa. However, nuclear translocation of β-catenin is often observed in various tumors, and such translocated β-catenin acts as a transcriptional factor to regulate the expression of its target genes [38,39]. Although we cannot explain exactly why SSA/P lesions with a nuclear β-catenin immunostaining pattern have higher proliferative ability, we speculate that Fn-associated β-catenin nuclear translocation may play at least some role in the proliferation of SSA/P lesions.…”

Section: Discussionmentioning

confidence: 77%

Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with Fusobacterium nucleatum

et al. 2021

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Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma–carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of β-catenin nuclear translocation and REG Iα expression.

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“…Transcription factors have a long-reported significant influence on the initiation, progression, invasion, metastasis, and therapy resistance of breast cancer ( 5 , 12 ). However, the prognostic value of whole TF members was poorly done.…”

Section: Discussionmentioning

confidence: 99%

“…Transcription factors (TFs) are proteins capable of binding DNA in a sequence-specific manner and regulating transcription ( 4 ). TFs are the mainstay of cancer because of their curial role in the initiation, progression, invasion, metastasis, and chemo-resistance of cancer ( 5 ). It is estimated that around 20% of oncogenes are identified as TFs ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Transcription Factor Prognostic Index for Breast Cancer

Liu

Zhou

et al. 2021

Front. Oncol.

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Transcription factors (TFs) are the mainstay of cancer and have a widely reported influence on the initiation, progression, invasion, metastasis, and therapy resistance of cancer. However, the prognostic values of TFs in breast cancer (BC) remained unknown. In this study, comprehensive bioinformatics analysis was conducted with data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We constructed the co-expression network of all TFs and linked it to clinicopathological data. Differentially expressed TFs were obtained from BC RNA-seq data in TCGA database. The prognostic TFs used to construct the risk model for progression free interval (PFI) were identified by Cox regression analyses, and the PFI was analyzed by the Kaplan-Meier method. A receiver operating characteristic (ROC) curve and clinical variables stratification analysis were used to detect the accuracy of the prognostic model. Additionally, we performed functional enrichment analysis by analyzing the differential expressed gene between high-risk and low-risk group. A total of nine co-expression modules were identified. The prognostic index based on 4 TFs (NR3C2, ZNF652, EGR3, and ARNT2) indicated that the PFI was significantly shorter in the high-risk group than their low-risk counterpart (p < 0.001). The ROC curve for PFI exhibited acceptable predictive accuracy, with an area under the curve value of 0.705 and 0.730. In the stratification analyses, the risk score index is an independent prognostic variable for PFI. Functional enrichment analyses showed that high-risk group was positively correlated with mTORC1 signaling pathway. In conclusion, the TF-related signature for PFI constructed in this study can independently predict the prognosis of BC patients and provide a deeper understanding of the potential biological mechanism of TFs in BC.

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Transcription Factors in Cancer Development and Therapy

Cited by 86 publications

References 259 publications

Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer

Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer

Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with Fusobacterium nucleatum

Identification of a Novel Transcription Factor Prognostic Index for Breast Cancer

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