Regulation of Breast Cancer-induced Bone Lesions by β-Catenin Protein Signaling

Chen, Yan; Shi, Heidi Y.; Stock, Stuart R.; Stern, Paula H.; Zhang, Ming

doi:10.1074/jbc.m111.294595

Cited by 31 publications

(19 citation statements)

References 43 publications

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Section: Discussionmentioning

confidence: 99%

“…Cellular signaling pathways, including the Wnt/β-catenin, ERK/MAPK, and PI3K/ Akt pathways, have been found to be aberrantly activated and play vital roles in the development and progression of breast cancer (35)(36)(37). Among these pathways, the prometastatic functions of Wnt/β-catenin signaling in breast cancer have been well documented (35,38). Notably, unlike in other cancer types, the mutations in β-catenin are rare, but the expression and/or nuclear localization of β-catenin is often abnormal in breast cancer, indicating a constitutive activation of Wnt/β-catenin signaling (9,39,40).…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

Cai¹,

Guan²,

Fang³

et al. 2013

J. Clin. Invest.

261

281

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Tumor metastasis involves a series of biological steps during which the tumor cells acquire the ability to invade surrounding tissues and survive outside the original tumor site. During the early stages, the cancer cells undergo an epithelial-mesenchymal transition (EMT). Wnt/β-catenin signaling is known to drive EMT and metastasis. Here we report that Wnt/β-catenin signaling is hyperactivated in metastatic breast cancer cells that express microRNA 374a (miR-374a). In breast cancer cell lines, ectopic overexpression of miR-374a promoted EMT and metastasis both in vitro and in vivo. Furthermore, miR-374a directly targeted and suppressed multiple negative regulators of the Wnt/β-catenin signaling cascade, including WIF1, PTEN, and WNT5A. Notably, miR-374a was markedly upregulated in primary tumor samples from patients with distant metastases and was associated with poor metastasis-free survival. These results demonstrate that miR-374a maintains constitutively activated Wnt/β-catenin signaling and may represent a therapeutic target for early metastatic breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

Cai¹,

Guan²,

Fang³

et al. 2013

J. Clin. Invest.

261

281

View full text Add to dashboard Cite

show abstract

“…WNT signaling promotes EMT associated with cancer progression. Nuclear β-catenin accumulation in the invasive fronts of primary tumors has been shown to lead to increased tumor metastasis [19,20]. Molecules targeting Wnt/β-catenin signaling can significantly inhibit tumor growth and EMT in many cancer types [21,22].…”

Section: Introductionmentioning

confidence: 99%

MSX1 inhibits cell migration and invasion through regulating the Wnt/β-catenin pathway in glioblastoma

Tao

Chen³

et al. 2015

Tumor Biol.

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Glioblastoma is a type of primary brain tumor with poor prognosis. The hallmark phenotype of glioblastoma is its aggressive invasion. Understanding the molecular mechanism of the invasion behavior of glioblastoma is essential for the development of effective treatment of the disease. In our present study, we found that the expression levels of a homeobox transcription factor, MSX1, were significantly reduced in glioblastoma compared to normal brain tissues. The levels of MSX1 in glioblastoma tissues were also correlated with the survival of the patients. In cultured glioblastoma cells, MSX1 was a negative regulator of cell migration and invasion. Loss of MSX1 enhanced cell migration and induced mesenchymal transition as characterized by the downregulation of E-cadherin and the upregulation of N-cadherin. Overexpression of MSX1 on the other hand led to the inhibition of both cell migration and mesenchymal transition. We also found that MSX1 was able to inhibit the Wnt/β-catenin signaling pathway, and that the ability to regulate the Wnt/β-catenin signaling pathway is critical for MSX1 to suppress glioblastoma cell migration and invasion.

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“…Consistent with this notion, expression of the extracellular inhibitor of Wnt/β-catenin signaling, secreted frizzled-related protein 1 (also known as SFRP1), which competes with the Wnt signaling receptor FZD for ligand binding, is significantly down-regulated in many breast cancers and is associated with poor survival and a poor therapeutic response151617. Recently, upregulation of the Wnt/β-catenin signaling pathway has also been shown to lead to increased tumor metastasis from the primary tumor181920.…”

mentioning

confidence: 99%

Blockade of Wnt/β-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype

Jang

Kim

Cho

et al. 2015

Sci Rep

298

241

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The identification of cancer stem cells (CSCs) represents an important milestone in the understanding of chemodrug resistance and cancer recurrence. More specifically, some studies have suggested that potential metastasis-initiating cells (MICs) might be present within small CSC populations. The targeting and eradication of these cells represents a potential strategy for significantly improving clinical outcomes. A number of studies have suggested that dysregulation of Wnt/β-catenin signaling occurs in human breast cancer. Consistent with these findings, our previous data have shown that the relative level of Wnt/β-catenin signaling activity in breast cancer stem cells (BCSCs) is significantly higher than that in bulk cancer cells. These results suggest that BCSCs could be sensitive to therapeutic approaches targeting Wnt/β-catenin signaling pathway. In this context, abnormal Wnt/β-catenin signaling activity may be an important clinical feature of breast cancer and a predictor of poor survival. We therefore hypothesized that Wnt/β-catenin signaling might regulate self-renewal and CSC migration, thereby enabling metastasis and systemic tumor dissemination in breast cancer. Here, we investigated the effects of inhibiting Wnt/β-catenin signaling on cancer cell migratory potential by examining the expression of CSC-related genes, and we examined how this pathway links metastatic potential with tumor formation in vitro and in vivo.

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Regulation of Breast Cancer-induced Bone Lesions by β-Catenin Protein Signaling

Cited by 31 publications

References 43 publications

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

MSX1 inhibits cell migration and invasion through regulating the Wnt/β-catenin pathway in glioblastoma

Blockade of Wnt/β-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype

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