Bone metastatic process of breast cancer involves methylation state affecting E-cadherin expression through TAZ and WWOX nuclear effectors

Matteucci, Emanuela; Maroni, Paola; Luzzati, Alessandro; Perrucchini, Giuseppe; Bendinelli, Paola; Desiderio, Maria Alfonsina

doi:10.1016/j.ejca.2012.05.006

Cited by 45 publications

(61 citation statements)

References 42 publications

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“…Increased expression or activation (nuclear localisation) during the metastatic cascade was also observed by comparing primary BC and bone metastases (Ref. 99). Finally, in a clinically focused study we showed that in non-metastatic BC with HER2 overexpression/amplification a TAZ-based score generated by combining staining intensity and cellular localisation (nuclear versus cytoplasmic) predicted pathological complete response (pCR) after neoadjuvant chemotherapy and trastuzumab (Ref.…”

Section: Clinical Implications: Taz and Yap Expression In Bcmentioning

confidence: 88%

The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications

Maugeri‐Saccà¹,

Barba²,

Pizzuti³

et al. 2015

Expert Rev. Mol. Med.

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The Hippo signalling is emerging as a tumour suppressor pathway whose function is regulated by an intricate network of intracellular and extracellular cues. Defects in the signal cascade lead to the activation of the Hippo transducers TAZ and YAP. Compelling preclinical evidence showed that TAZ/YAP are often aberrantly engaged in breast cancer (BC), where their hyperactivation culminates into a variety of tumour-promoting functions such as epithelial-to-mesenchymal transition, cancer stem cell generation and therapeutic resistance. Having acquired a more thorough understanding in the biology of TAZ/YAP, and the molecular outputs they elicit, has prompted a first wave of exploratory, clinically-focused analyses aimed at providing initial hints on the prognostic/predictive significance of their expression. In this review, we discuss oncogenic activities linked with TAZ/YAP in BC, and we propose clinical strategies for investigating their role as biomarkers in the clinical setting. Finally, we address the therapeutic potential of TAZ/YAP targeting and the modalities that, in our opinion, should be pursued in order to further study the biological and clinical consequences of their inhibition.

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Section: Clinical Implications: Taz and Yap Expression In Bcmentioning

confidence: 88%

The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications

Maugeri‐Saccà¹,

Barba²,

Pizzuti³

et al. 2015

Expert Rev. Mol. Med.

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“…TAZ, a paralogue of YAP in mammals, was recently reported to facilitate HIF1α activity 29,30 , but the molecular mechanism was not clear. We were interested to investigate the effect of YAP on hypoxia response and found that YAP knockdown greatly decreased hypoxiainduced HIF1α accumulation (Fig.…”

mentioning

confidence: 98%

Hypoxia regulates Hippo signalling through the SIAH2 ubiquitin E3 ligase

et al. 2014

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The Hippo signalling pathway plays important roles in animal development, physiology and tumorigenesis. Understanding how the activity of this pathway is regulated by the cellular microenvironment remains a major challenge. Here we elucidate a molecular mechanism by which hypoxia deactivates Hippo signalling. We demonstrate that the E3 ubiquitin ligase SIAH2 stimulates YAP by destabilizing LATS2, a critical component of the Hippo pathway, in response to hypoxia. Loss of SIAH2 suppresses tumorigenesis in a LATS2-dependent manner in a xenograft mouse model. We further show that YAP complexes with HIF1α and is essential for HIF1α stability and function in tumours in vivo. LATS2 is downregulated in human breast tumours and negatively correlates with SIAH2 expression levels, indicating that the SIAH2-LATS2 pathway may have a role in human cancer. Our data uncover oxygen availability as a microenvironment signal for the Hippo pathway and have implications for understanding the regulation of Hippo signalling in tumorigenesis.

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“…The expression levels and activity of TAZ are frequently upregulated in high-grade metastatic breast cancer (16)(17)(18). Activation of YAP induces epithelial to mesenchymal transition and promotes breast tumor metastasis (19,20).…”

Section: Introductionmentioning

confidence: 99%

Genetic variations in the Hippo signaling pathway and breast cancer risk in African American women in the AMBER Consortium

Zhang

Yao

et al. 2016

CARCIN

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The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. Dysfunction of the Hippo pathway components has been linked with breast cancer stem cell regulation, as well as breast tumor progression and metastasis. TAZ, a key component of the Hippo pathway, is highly expressed in triple negative breast cancer; however, the associations of genetic variations in this important pathway with breast cancer risk remain largely unexplored. Here, we analyzed 8309 germline variants in 15 genes from the Hippo pathway with a total of 3663 cases and 4687 controls from the African American Breast Cancer Epidemiology and Risk Consortium. Odds ratios (ORs) were estimated using logistic regression for overall breast cancer, by estrogen receptor (ER) status (1983 ER positive and 1098 ER negative), and for case-only analyses by ER status. The Hippo signaling pathway was significantly associated with ER-negative breast cancer (pathway level P = 0.02). Gene-based analyses revealed that CDH1 was responsible for the pathway association (P < 0.01), with rs4783673 in CDH1 statistically significant after genelevel adjustment for multiple comparisons (P = 9.2 × 10 −5 , corrected P = 0.02). rs142697907 in PTPN14 was associated with ER-positive breast cancer and rs2456773 in CDK1 with ER-negativity in case-only analysis after gene-level correction for multiple comparisons (corrected P < 0.05). In conclusion, common genetic variations in the Hippo signaling pathway may contribute to both ER-negative and ER+ breast cancer risk in AA women.

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Bone metastatic process of breast cancer involves methylation state affecting E-cadherin expression through TAZ and WWOX nuclear effectors

Cited by 45 publications

References 42 publications

The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications

The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications

Hypoxia regulates Hippo signalling through the SIAH2 ubiquitin E3 ligase

Genetic variations in the Hippo signaling pathway and breast cancer risk in African American women in the AMBER Consortium

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