FOXC1-induced Gli2 activation: A non-canonical pathway contributing to stemness and anti-Hedgehog resistance in basal-like breast cancer

Han, Bangwoo; Qu, Ying; Yu-Rice, Yi; Johnson, Jeffrey; Cui, Xiaojiang

doi:10.1080/23723556.2015.1131668

Cited by 10 publications

(11 citation statements)

References 12 publications

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“…We found that 139 genes were positively and 108 genes negatively correlated with ST8SIA1 (Supplementary Figure 2). Among these genes, those associated with BCSC function include BCL11A (25) (Pearson’s r = 0.645) and FOXC1 (26, 27) (Pearson’s r = 0.61), both of which were highly positively correlated with ST8SIA1 expression (Fig 2C). In addition, tumor suppressor gene GATA3 (28) (Pearson’s r = −0.583) and its closely associated protein FOXA1 (29) (Pearson’s r = −0.615) were highly negatively correlated with ST8SIA1 (Fig 2C).…”

Section: Resultsmentioning

confidence: 99%

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ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK–AKT–mTOR Signaling Pathway

Nguyen

Yan

Yuan

et al. 2018

Molecular Cancer Therapeutics

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Breast cancer stem-like cells (BCSCs) are implicated in cancer recurrence and metastasis of triple negative breast cancer (TNBC). We have recently discovered that ganglioside GD2 expression defines BCSCs and that ST8SIA1 regulates GD2 expression and BCSC function. In this report, we show that ST8SIA1 is highly expressed in primary TNBC; its expression is positively correlated with the expression of several BCSC associated genes such as BCL11A, FOXC1, CXCR4, PDGFRβ, SOX2 and mutations in p53. CRISPR knockout of ST8SIA1 completely inhibited BCSC functions, including in vitro tumorigenesis and mammosphere formation. Mechanistic studies discovered activation of the FAK-AKT-mTOR signaling pathway in GD2+ BCSCs, and its tight regulation by ST8SIA1. Finally, knockout of ST8SIA1 completely blocked in vivo tumor growth and metastasis by TNBC cells. In summary, this data demonstrates the mechanism by which ST8SIA1 regulates tumor growth and metastasis in TNBC and identifies it as a novel therapeutic target.

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Section: Resultsmentioning

confidence: 99%

“…These genes include BCL11A, PDGFRβ, VCAM1, PDGFRα, SOX2, FOXC1, CXCR4, CXCL12, and FGFR2. BCL11A and FOXC1 have been reported to be upregulated in BCSCs and to regulate their function (25, 27). We have previously shown that induction of EMT enhances PDGFRβ expression in breast epithelial cells (42).…”

Section: Discussionmentioning

confidence: 99%

ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK–AKT–mTOR Signaling Pathway

Nguyen

Yan

Yuan

et al. 2018

Molecular Cancer Therapeutics

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“… 82 Binding of FOXC1 to Gli2, an ultimate downstream molecule of Hh, is specifically required for the activation of Hh signaling. 81 , 83 Therefore, inactivation of Gli2 and blockage of the Hh pathway might be potential ways to attenuate FOXC1-induced tumorigenicity.…”

Section: Foxc1-targeted Processes In Tumorsmentioning

confidence: 99%

FOXC1 in cancer development and therapy: deciphering its emerging and divergent roles

et al. 2017

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Forkhead box C1 (FOXC1) is an essential member of the forkhead box transcription factors and has been highlighted as an important transcriptional regulator of crucial proteins associated with a wide variety of carcinomas. FOXC1 regulates tumor-associated genes and is regulated by multiple pathways that control its mRNA expression and protein activity. Aberrant FOXC1 expression is involved in diverse tumorigenic processes, such as abnormal cell proliferation, cancer stem cell maintenance, cancer migration, and angiogenesis. Herein, we review the correlation between the expression of FOXC1 and tumor behaviors. We also summarize the mechanisms of the regulation of FOXC1 expression and activity in physiological and pathological conditions. In particular, we focus on the pathological processes of cancer targeted by FOXC1 and discuss whether FOXC1 is good or detrimental during tumor progression. Moreover, FOXC1 is highlighted as a clinical biomarker for diagnosis or prognosis in various human cancers. The information reviewed here should assist in experimental designs and emphasize the potential of FOXC1 as a therapeutic target for cancer.

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“…Osteosarcoma stem cells contribute to tumour recurrence, metastasis, and drug resistance via their self-renewal and differentiation 60 . The Forkhead box C1 (FOXC1) transcription factor promotes CSC properties in basal-like breast cancer, which could activate Smo-independent Hh signalling and Gli2, and provides novel insight into anti-Hh therapy resistance in cancer progression 61 . In human pancreatic CSCs, Ski has a key role in promoting tumour progression.…”

Section: Introduction Of Hedgehog Signalling Pathwaymentioning

confidence: 99%

Hedgehog signalling in the tumourigenesis and metastasis of osteosarcoma, and its potential value in the clinical therapy of osteosarcoma

et al. 2018

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The Hedgehog (Hh) signalling pathway is involved in cell differentiation, growth and tissue polarity. This pathway is also involved in the progression and invasion of various human cancers. Osteosarcoma, a subtype of bone cancer, is commonly seen in children and adolescents. Typically, pulmonary osteosarcoma metastases are especially difficult to control. In the present paper, we summarise recent studies on the regulation of osteosarcoma progression and metastasis by downregulating Hh signalling. We also summarise the crosstalk between the Hh pathway and other cancer-related pathways in the tumourigenesis of various cancers. We further summarise and highlight the therapeutic value of potential inhibitors of Hh signalling in the clinical therapy of human cancers.

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FOXC1-induced Gli2 activation: A non-canonical pathway contributing to stemness and anti-Hedgehog resistance in basal-like breast cancer

Cited by 10 publications

References 12 publications

ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK–AKT–mTOR Signaling Pathway

ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK–AKT–mTOR Signaling Pathway

FOXC1 in cancer development and therapy: deciphering its emerging and divergent roles

Hedgehog signalling in the tumourigenesis and metastasis of osteosarcoma, and its potential value in the clinical therapy of osteosarcoma

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