ZFHX3 Promotes the Proliferation and Tumor Growth of ER-Positive Breast Cancer Cells Likely by Enhancing Stem-Like Features and MYC and TBX3 Transcription

Dong, Ge; Ma, Guansheng; Wu, Rui; Liu, Mingcheng; Gao, Ang; Li, Xiawei; Ai, Jun; Liu, Xiaoyu; Zhang, Zhiqian; Zhang, Baotong; Fu, Liwei; Dong, Jin‐Tang

doi:10.3390/cancers12113415

Cited by 17 publications

(12 citation statements)

References 72 publications

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“…Tbox transcription factor 3 (Tbx3) through FGF signaling is associated with BCSC phenotypes and oncogenesis [118,119]. In addition, the ZFHX3 transcription factor by enhancing TBX3 transcription increases the proliferation and tumor growth of BCSCs [120]. A recent study indicated that Runt-related transcription factor 2 (RUNX2) by activating the PI3K/AKT pathway contributes to tumorigenicity, metastasis, and EMT in BCSCs [121].…”

Section: Pi3k-akt Signalingmentioning

confidence: 99%

Signaling pathways governing breast cancer stem cells behavior

Song¹,

Farzaneh

2021

Stem Cell Res Ther

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Breast cancer is the second common cancer and the leading cause of malignancy among females overall. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that play a critical role in the metastasis of breast cancer to other organs in the body. BCSCs have both self-renewal and differentiation capacities, which are thought to contribute to the aggressiveness of metastatic lesions. Therefore, targeting BCSCs can be a suitable approach for the treatment and metastasis of breast cancer. Growing evidence has indicated that the Wnt, NFκB, Notch, BMP2, STAT3, and hedgehog (Hh) signaling pathways govern epithelial-to-mesenchymal transition (EMT) activation, growth, and tumorigenesis of BCSCs in the primary regions. miRNAs as the central regulatory molecules also play critical roles in BCSC self-renewal, metastasis, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for breast cancer diagnosis and therapy. This review discusses known signaling mechanisms involved in the stimulation or prevention of BCSC self-renewal, metastasis, and tumorigenesis.

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Section: Pi3k-akt Signalingmentioning

confidence: 99%

Signaling pathways governing breast cancer stem cells behavior

Song¹,

Farzaneh

2021

Stem Cell Res Ther

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“…ZFHX3 encodes a large transcription factor containing multiple motifs, including 23 zinc-finger domains, and inactivating mutations of this gene are frequently observed in metastatic or high-grade human prostate cancers, 28 but promotes tumour growth of liver cancer cells 29 and proliferation of breast cancer cells by upregulating MYC proto-oncogene, basic helix-loop-helix transcription factor (MYC), T-box transcription factor 3 (TBX3) and others. 30 NCOA2 encodes a transcriptional regulator of nuclear receptors that plays a key role in regulation of energy balance, affecting different physiological processes such as cell growth and energy metabolism 31 and is involved in the development, progression, and metastasis of many malignant tumours. 32 The TET2 gene encodes a methylcytosine dioxygenase that catalyses the conversion of methylcytosine to 5hydroxymethylcytosine, playing critical roles in epigenetic regulation of haematopoietic progenitor cells and affects both myeloid and lymphoid lineages.…”

Section: Discussionmentioning

confidence: 99%

“…ZFHX3 encodes a large transcription factor containing multiple motifs, including 23 zinc‐finger domains, and inactivating mutations of this gene are frequently observed in metastatic or high‐grade human prostate cancers, 28 but promotes tumour growth of liver cancer cells 29 and proliferation of breast cancer cells by upregulating MYC proto‐oncogene, basic helix‐loop‐helix transcription factor ( MYC ), T‐box transcription factor 3 ( TBX3 ) and others 30 …”

Section: Discussionmentioning

confidence: 99%

Characteristics of genetic alterations of peripheral T‐cell lymphoma in childhood including identification of novel fusion genes: the Japan Children’s Cancer Group (JCCG)

et al. 2021

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Summary Peripheral T‐cell lymphoma (PTCL) is a group of heterogeneous non‐Hodgkin lymphomas showing a mature T‐cell or natural killer cell phenotype, but its molecular abnormalities in paediatric patients remain unclear. By employing next‐generation sequencing and multiplex ligation‐dependent probe amplification of tumour samples from 26 patients, we identified somatic alterations in paediatric PTCL including Epstein–Barr virus (EBV)‐negative (EBV–) and EBV‐positive (EBV+) patients. As recurrent mutational targets for PTCL, we identified several previously unreported genes, including TNS1, ZFHX3, LRP2, NCOA2 and HOXA1, as well as genes previously reported in adult patients, e.g. TET2, CDKN2A, STAT3 and TP53. However, for other reported mutations, VAV1‐related abnormalities were absent and mutations of NRAS, GATA3 and JAK3 showed a low frequency in our cohort. Concerning the association of EBV infection, two novel fusion genes: STAG2‐AFF2 and ITPR2‐FSTL4, and deletion and alteration of CDKN2A/2B, LMO1 and HOXA1 were identified in EBV– PTCL, but not in EBV+ PTCL. Conversely, alterations of PCDHGA4, ADAR, CUL9 and TP53 were identified only in EBV+ PTCL. Our observations suggest a clear difference in the molecular mechanism of onset between paediatric and adult PTCL and a difference in the characteristics of genetic alterations between EBV– and EBV+ paediatric PTCL.

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“…Many studies have investigated the role of TFs in tumors and the corresponding mechanisms. Dong et al found that the transcription factor can support the development of breast cancer (Dong et al, 2020). Zhan et al reported that transcription factors play a key role in the development of hepatoblastoma (Zhan & Zhao, 2020).…”

Section: Discussionmentioning

confidence: 99%

Identification of Transcription Factor-Related Gene Signature and Risk Score Model for Colon Adenocarcinoma

Lin

Cao

et al. 2021

Front. Genet.

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The prognosis of colon adenocarcinoma (COAD) remains poor. However, the specific and sensitive biomarkers for diagnosis and prognosis of COAD are absent. Transcription factors (TFs) are involved in many biological processes in cells. As the molecule of the signal pathway of the terminal effectors, TFs play important roles in tumorigenesis and development. A growing body of research suggests that aberrant TFs contribute to the development of COAD, as well as to its clinicopathological features and prognosis. In consequence, a few studies have investigated the relationship between the TF-related risk model and the prognosis of COAD. Therefore, in this article, we hope to develop a prognostic risk model based on TFs to predict the prognosis of patients with COAD. The mRNA transcription data and corresponding clinical data were downloaded from TCGA and GEO. Then, 141 differentially expressed genes, validated by the GEPIA2 database, were identified by differential expression analysis between normal and tumor samples. Univariate, multivariate and Lasso Cox regression analysis were performed to identify seven prognostic genes (E2F3, ETS2, HLF, HSF4, KLF4, MEIS2, and TCF7L1). The Kaplan–Meier curve and the receiver operating characteristic curve (ROC, 1-year AUC: 0.723, 3-year AUC: 0.775, 5-year AUC: 0.786) showed that our model could be used to predict the prognosis of patients with COAD. Multivariate Cox analysis also reported that the risk model is an independent prognostic factor of COAD. The external cohort (GSE17536 and GSE39582) was used to validate our risk model, which indicated that our risk model may be a reliable predictive model for COAD patients. Finally, based on the model and the clinicopathological factors, we constructed a nomogram with a C-index of 0.802. In conclusion, we emphasize the clinical significance of TFs in COAD and construct a prognostic model of TFs, which could provide a novel and reliable model for the prognosis of COAD.

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ZFHX3 Promotes the Proliferation and Tumor Growth of ER-Positive Breast Cancer Cells Likely by Enhancing Stem-Like Features and MYC and TBX3 Transcription

Cited by 17 publications

References 72 publications

Signaling pathways governing breast cancer stem cells behavior

Signaling pathways governing breast cancer stem cells behavior

Characteristics of genetic alterations of peripheral T‐cell lymphoma in childhood including identification of novel fusion genes: the Japan Children’s Cancer Group (JCCG)

Identification of Transcription Factor-Related Gene Signature and Risk Score Model for Colon Adenocarcinoma

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