The Hippo signaling pathway and stem cell biology

Ramos, Azucena; Camargo, Fernando D.

doi:10.1016/j.tcb.2012.04.006

Cited by 252 publications

(241 citation statements)

References 84 publications

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“…This protocol was described previously [53]. Three germarium phenotypes, normal-like germaria (number of Sp: 2-7), moderate tumorous germaria (number of Sp: [8][9][10][11][12][13][14][15][16][17][18][19][20] and severe tumorous germaria (number of Sp: > 20), used for statistic assays were shown in Figure 2A-2C.…”

Section: Phenotypic Analysismentioning

confidence: 99%

“…The Hippo signaling pathway features a kinase cascade comprising the Ste20-like kinase Hippo (Hpo), the nuclear Dbf-2-related (NDR) family kinase Warts (Wts), and their scaffold proteins, Salvador (Sav) and Mob as tumor suppressor (Mats). Hpo phosphorylates and activates Wts, which in turn phosphorylates the transcriptional co-activator Yorkie (Yki), leading to its cytoplasmic retention and inactivation [13,15,[19][20][21]. In the absence of the upstream kinase cascade signaling, Yki is therefore released from the control of Hippo signaling and translocates into the nucleus, where it binds to the transcription factor, Scalloped (Sd), to activate downstream target genes including diap1, cyclin E and bantam, thereby promoting cell proliferation and inhibiting cell apoptosis [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, activation of the Hippo pathway turns off the nuclear functions of Yki and thus maintains Sd-mediated default transcriptional repression, which precludes cell growth [24,25]. Thus, balanced regulation of Yki activation and Sd-mediated default repression is critical for organ size control during development, and is possibly important in other biological processes such as stem cell regulation and tumorigenesis [13,20].…”

Section: Introductionmentioning

confidence: 99%

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Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

Kan

Chen

et al. 2015

Cell Res

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Section: Phenotypic Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

Kan

Chen

et al. 2015

Cell Res

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“…Previous studies on the regulation of the development and size of mammals (9)(10)(11) indicated that the Hippo pathway was quite conservative. It was also demonstrated that abnormal functions of Hippo pathway were closely associated with the occurrence, development and prognosis of tumors (12,13), which has become a popular subject of cancer research.…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of YAP in laryngeal squamous cell carcinoma patients

Qiu

Dong

et al. 2016

Oncology Letters

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Abstract. The aim of the present study was to investigate the expression levels of Yes-associated protein (YAP) in different grades of laryngeal squamous cell carcinoma (LSCC) tissues and vocal cord polyps tissues, and to investigate any correlations with clinical factors. The expression of YAP in 128 cases of LSCC and 10 cases of vocal cord polyps tissues was tested using immunohistochemistry. YAP was primarily present in the nucleus of LSCC and controls, whereas phosphorylated YAP expression was present in the cytoplasm. The results indicated that YAP expression was upregulated in LSCC samples compared with vocal cord polyps tissues. YAP expression was positively correlated with the malignant degree of LSCC (P<0.01) and a high level of YAP expression in LSCC tissues was correlated with pathological type, lymphatic metastasis and clinical stage. The present study provided evidence for the expression and localization of YAP in LSCC and vocal cord polyps tissues. Thus, YAP may be involved in the occurrence and development of LSCC as an oncogene. IntroductionLaryngeal carcinoma is a common malignant tumor in otolaryngology that seriously endangers physical and mental health (1). The incidence of laryngeal malignant tumors is ~1-5% of all whole body malignant tumors and is ranked third of all otolaryngology malignant tumors. Laryngeal squamous cell carcinoma (LSCC) accounts for 95% of laryngeal carcinoma and tends to occur in middle-aged and older males (2). Due to the early presence of hoarseness (3), glottic carcinoma can be detected timely. However, it brings challenges for the diagnosis of LSCC owing to the unapparent symptoms in the early stage of supraglottic and subglottic carcinomas (4). Early diagnosis and treatment of LSCC are critical in improving the 5-year survival rate and quality of life of patients (5-7).The Hippo pathway was originally observed to be a key pathway that is involved in the regulation of the size of organs of Drosophila melanogaster by regulating cell proliferation and apoptosis (8). Previous studies on the regulation of the development and size of mammals (9-11) indicated that the Hippo pathway was quite conservative. It was also demonstrated that abnormal functions of Hippo pathway were closely associated with the occurrence, development and prognosis of tumors (12,13), which has become a popular subject of cancer research.The aim of the present study was to investigate the expression and localization of YAP in LSCC and vocal cord polyps tissues as well as the clinical significance thereof. Materials and methodsSample collection. Approval for the present study was obtained from the Human Research Ethics Committee of Lihuili Hospital, Ningbo, China. Prior to sample collection, the patients and their family members were informed with regard to the process of the study and the possible risks. Tissues were collected from 128 patients with LSCC and 10 patients with vocal cord polyps between January 2009 and January 2013 at the Ningbo University Affiliated Lihuili Hospital. All patients s...

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“…This stimulation is inhibited by Hippo signalling, which regulates organ size, cell proliferation, differentiation and stem cell self-renewal. [12][13][14][15] Several components are involved in the transduction of the signal. In Drosophila, Hippo and its regulatory protein Salvador stimulate Warts, which inactivates Yorkie.…”

mentioning

confidence: 99%

Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

et al. 2014

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TAZ, a transcriptional modulator, has a key role in cell proliferation, differentiation and stem cell self-renewal. TAZ activity is regulated by several signalling pathways, including Hippo, GPCR and Wnt signalling, but the regulatory mechanisms of TAZ activation are not yet clearly understood. In this report, we show that TAZ is regulated by canonical Wnt signalling during osteogenic differentiation. Wnt3a increases TAZ expression and an inhibitor of GSK3b, a downstream effector of Wnt signalling, induces TAZ. Wnt3a facilitates the dephosphorylation of TAZ, which stabilises TAZ and prevents it from binding 14-3-3 proteins, thus inducing the nuclear localisation of TAZ. Dephosphorylation of TAZ occurs via PP1A, and depletion of PP1A blocks Wnt3a-induced TAZ stabilisation. Wnt3a-induced TAZ activates osteoblastic differentiation and siRNA-induced TAZ depletion decreases Wnt3a-induced osteoblast differentiation. Taken together, these results show that TAZ mediates Wnt3a-stimulated osteogenic differentiation through PP1A, suggesting that the Wnt signal regulates the Hippo pathway. Transcriptional co-activator with PDZ-binding motif (TAZ, also known as WWTR1) is a transcriptional modulator that has a key role in cell proliferation, differentiation and stem cell selfrenewal. TAZ interacts with several transcription factors including Runx2, PPARg, TEADS, TTF-1/Nkx2.1, Tbx5, Pax3, Smad2/3-4 complexes, MyoD and NFAT5. [1][2][3][4][5][6][7][8][9][10][11] This interaction regulates the transcription of target genes with diverse biological functions. For example, TAZ and its paralogue YAP interact with TEADs and stimulate their target genes, including CTGF and Cyr61, to promote cell proliferation and migration. This stimulation is inhibited by Hippo signalling, which regulates organ size, cell proliferation, differentiation and stem cell self-renewal.12-15 Several components are involved in the transduction of the signal. In Drosophila, Hippo and its regulatory protein Salvador stimulate Warts, which inactivates Yorkie. These components are highly evolutionarily conserved and their mammalian orthologues have been characterised. MST1/2 and its regulatory protein WW45 stimulate the downstream kinase Lats1/2, which inhibits nuclear localisation of TAZ/YAP and induces their proteolytic degradation.In cellular differentiation, TAZ modulates the cellular fate of mesenchymal stem cells (MSCs) via the activation of osteoblast and myoblast differentiation, and the inhibition of adipocytes differentiation. 2,10 The interaction between TAZ and Runx2 stimulates Runx2-mediated gene transcription. Wnts are a family of secreted glycoproteins that are involved in the regulation of cell proliferation, differentiation, axis formation, organ development and tissue homeostasis. 16-18b-Catenin is a transcriptional regulator in the canonical Wnt pathway, and, in the absence of Wnts, cytoplasmic b-catenin is phosphorylated by casein kinase I (CKI) and glycogen synthase kinase 3b (GSK3b). This phosphorylation facilitates its ubiquitination and pr...

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The Hippo signaling pathway and stem cell biology

Cited by 252 publications

References 84 publications

Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

Expression and clinical significance of YAP in laryngeal squamous cell carcinoma patients

Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

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