Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma

Bouvier, Corinne; Macagno, Nicolas; Nguyen, Quoc-Tuan; Loundou, Anderson; Jiguet-Jiglaire, Carine; Gentet, Jean‐Claude; Jouve, Jean-Luc; Rochwerger, Alexandre; Mattei, Jean-Camille; Bouvard, Daniel; Salas, Sébastien

doi:10.18632/oncotarget.11876

Cited by 53 publications

(48 citation statements)

References 32 publications

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“…The lack of association in our study may be because of the small sample size. A recent study found that YAP/TAZ immunoreactive score was correlated with overall survival of osteosarcoma patients . Among the five mesothelioma cell lines we studied, three (211H, H2052 and H290) showed both decreased phosphorylation of YAP (Ser127) to YAP ratio and increased GTIIC reporter activity.…”

Section: Discussionmentioning

confidence: 86%

Targeting YAP in malignant pleural mesothelioma

Zhang

Dai

Hsu

et al. 2017

J Cellular Molecular Medi

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Malignant mesothelioma is an aggressive cancer that is resistant to current therapy. The poor prognosis of mesothelioma has been associated with elevated Yes‐associated protein (YAP) activity. In this study, we evaluated the effect of targeting YAP in mesothelioma. First, we comprehensively studied YAP activity in five mesothelioma cell lines (211H, H2052, H290, MS‐1 and H2452) and one normal mesothelial cell line (LP9). We found decreased phospho‐YAP to YAP protein ratio and consistently increased GTIIC reporter activity in 211H, H2052 and H290 compared to LP9. The same three cell lines (IC50s < 1 μM) were more sensitive than LP9 (IC50 = 3.5 μM) to the YAP/TEAD inhibitor verteporfin. We also found that verteporfin significantly reduced YAP protein level, mRNA levels of YAP downstream genes and GTIIC reporter activity in the same three cell lines, indicating inhibition of YAP signaling by verteporfin. Verteporfin also impaired invasion and tumoursphere formation ability of H2052 and H290. To validate the effect of specific targeting YAP in mesothelioma cells, we down‐regulated YAP by siRNA. We found siYAP significantly decreased YAP transcriptional activity and impaired invasion and tumoursphere formation ability of H2052 and H290. Furthermore, forced overexpression of YAP rescued GTIIC reporter activity and cell viability after siYAP targeting 3′UTR of YAP. Finally, we found concurrent immunohistochemistry staining of ROCK2 and YAP (P < 0.05). Inhibition of ROCK2 decreased GTIIC reporter activity in H2052 and 211H suggesting that Rho/ROCK signaling also contributed to YAP activation in mesothelioma cells. Our results indicate that YAP may be a potential therapeutic target in mesothelioma.

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Section: Discussionmentioning

confidence: 86%

Targeting YAP in malignant pleural mesothelioma

Zhang

Dai

Hsu

et al. 2017

J Cellular Molecular Medi

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“…Immunohistochemically, high YAP expression was noted in 60% to 85% of osteosarcomas [184][185][186][187], but only nuclear immunoreactivity in 30% to 46% of cases correlated with an adverse outcome (observed in some [184,185] but not all studies, potentially due to small patient cohorts [186,188]). Metastatic events were either not [186] or only slightly more frequent in patients with nuclear YAP (53%) than in those lacking nuclear YAP immunoreactivity (36%) [185].…”

Section: Yap/taz In Osteosarcomamentioning

confidence: 98%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.Cells 2020, 9, 972 2 of 34 co-activators Yes-associated protein 1 (YAP-1, YAP) and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1), which are typically controlled on the post-translational level by upstream regulatory signaling pathways in organ development and tissue homeostasis [2,3]. YAP and TAZ were reported to affect self-renewal and lineage commitment of stem cells [4][5][6][7], while hyperactivation of YAP and TAZ have been linked to cancer growth and metastasis in various tumors [8][9][10]. TAZ levels are elevated in approximately 20% of cancers and drive invasion and metastasis [11,12], while YAP is frequently overexpressed or amplified in cancer and was shown to promote resistance to chemotherapy in oncogene-addicted tumors up...

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“…Literature on OS is less scarce than on EWs. Aberrations in Hippo signaling pathway were demonstrated in OS using immunochemistry approaches; this demonstrated a nuclear localization of YAP in OS patient tumor biopsies [90,91]. Interestingly, Bouvier and Coll have proven a correlation between YAP nuclear localization and a poor prognosis, allowing for the establishment of a vital prognostic at diagnosis [90].…”

Section: Osteosarcomamentioning

confidence: 99%

Hippo/YAP Signaling Pathway: A Promising Therapeutic Target in Bone Paediatric Cancers?

Morice

Danieau

Rédini

et al. 2020

Cancers

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Osteosarcoma and Ewing sarcoma are the most prevalent bone pediatric tumors. Despite intensive basic and medical research studies to discover new therapeutics and to improve current treatments, almost 40% of osteosarcoma and Ewing sarcoma patients succumb to the disease. Patients with poor prognosis are related to either the presence of metastases at diagnosis or resistance to chemotherapy. Over the past ten years, considerable interest for the Hippo/YAP signaling pathway has taken place within the cancer research community. This signaling pathway operates at different steps of tumor progression: Primary tumor growth, angiogenesis, epithelial to mesenchymal transition, and metastatic dissemination. This review discusses the current knowledge about the involvement of the Hippo signaling pathway in cancer and specifically in paediatric bone sarcoma progression.

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Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma

Cited by 53 publications

References 32 publications

Targeting YAP in malignant pleural mesothelioma

Targeting YAP in malignant pleural mesothelioma

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Hippo/YAP Signaling Pathway: A Promising Therapeutic Target in Bone Paediatric Cancers?

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