YAP triggers the Wnt/β-catenin signalling pathway and promotes enterocyte self-renewal, regeneration and tumorigenesis after DSS-induced injury

Deng, Feihong; Peng, Liang; Li, Zhijun; Gao, Tieren; Liang, Erbo; Chen, Shengbo; Zhao, Xinmei; Zhi, Fachao

doi:10.1038/s41419-017-0244-8

Cited by 164 publications

(138 citation statements)

References 47 publications

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“…There is emerging evidence that physiological Hippo signaling is not only important for anti-pathogenic immunity but also might serve to link the activation and resolution phases of an immune response. In the context of tissue injury, Hippo signaling may be differentially regulated by multiple inputs, including contact inhibition, mechanotransduction and inflammatory mediators [ 61 ]. In their description of Yki-induced Upd3 expression, Houtz et al showed that Yki and Scalloped function within a Misshapen (Msn)-Wts-Yorkie/Scalloped-Upd3 signaling axis that enhances intestinal tissue renewal during the Drosophila midgut response to Ecc15 bacterial infection [ 55 ].…”

Section: Hippo Signaling Is Part Of An Immune Responsementioning

confidence: 99%

The Hippo Pathway: Immunity and Cancer

Taha

Rensburg

Yang

2018

Cancers

131

101

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Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

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Section: Hippo Signaling Is Part Of An Immune Responsementioning

confidence: 99%

The Hippo Pathway: Immunity and Cancer

Taha

Rensburg

Yang

2018

Cancers

131

101

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“…Recently, the Hippo pathway has been reported to be connected to Wnt/β-catenin signaling. The Hippo signal transducer YAP/TAZ is part of the β-catenin disruption complex, which can coordinate the Wnt/β-catenin response regulating stem cell self-renewal and tissue homeostasis ( Deng et al, 2018 ). In cancer cells, the downregulation of Hippo signaling is linked to the upregulation of β-catenin activity.…”

Section: The Wnt/β-catenin Signaling Pathway and The Hippo Signaling mentioning

confidence: 99%

Regulatory Mechanisms of the Wnt/β-Catenin Pathway in Diabetic Cutaneous Ulcers

et al. 2018

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Skin ulcers are a serious complication of diabetes. Diabetic patients suffer from vascular lesions and complications such as peripheral neuritis, peripheral vascular lesions, and collagen abnormalities, which result in skin wounds that are refractory and often develop into chronic ulcers. The healing of skin ulcers requires an inflammatory reaction, wound proliferation, remodeling regulation, and control of stem cells. Studies investigating diabetic cutaneous ulcers have focused on cellular and molecular levels. Diabetes can cause nerve and blood vessel damage, and persistent high blood sugar levels can cause systemic multisite nerve damage based on peripheral neuropathy. The long-term hyperglycemia state enables the polyol glucose metabolism pathway to be activated, increasing the accumulation of toxic substances in the vascular injured nerve tissue cells. Sustained hyperglycemia leads to dysfunction of epithelial cells, leading to a decrease in pro-angiogenic signaling and nitric oxide production. In addition, due to impaired leukocyte function in hyperglycemia, immune function is impaired and the immune response at relevant sites is insufficient, making diabetic foot more difficult to heal. The Wnt/β-catenin pathway is a highly conserved signal transduction pathway involved in a variety of biological processes, such as cell proliferation, apoptosis, and differentiation. It is considered an important pathway involved in the healing of skin wounds. This article summarizes the mechanism of action of the Wnt/β-catenin pathway involved in the inflammatory responses to diabetic ulcers, wound proliferation, wound remodeling, and stem cells. The interactions between the Wnt signal pathway and other metabolic pathways are also discussed.

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“…YAP and TAZ can also reduce sensitivity to DNA damaging agents by upregulating signaling which bypass cell cycle checkpoints induced by DNA damage, or by upregulating pro-survival and pro-proliferative signaling, typically hyperactivated in cells with stemness properties, where YAP/TAZ are often overexpressed and whose number increases over the course of radiotherapy and chemotherapy to repopulate the tumor mass [ 208 ]. It has also been shown that hyperactivation of β-catenin signaling can increase chemoresistance and radioresistance in different cancer types [ 209 , 210 , 211 ], and a synergism between β-catenin and YAP/TAZ has been described in cancer, including lung cancer [ 64 , 212 , 213 , 214 ], suggesting a possible role of YAP and TAZ in chemoresistance and radioresistance through its crosstalk with β-catenin signaling that needs to be further investigated in lung cancer. All the mechanisms described above can explain how cancer cells overexpressing YAP and/or TAZ can bypass the inhibitory effect of cytotoxic chemotherapy and radiotherapy.…”

Section: Synergism Between Yap/taz Inhibition and Current Therapiementioning

confidence: 99%

YAP and TAZ in Lung Cancer: Oncogenic Role and Clinical Targeting

Sardo¹,

Strano²,

Blandino³

2018

Cancers

102

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Lung cancer is the leading cause of cancer death in the world and there is no current treatment able to efficiently treat the disease as the tumor is often diagnosed at an advanced stage. Moreover, cancer cells are often resistant or acquire resistance to the treatment. Further knowledge of the mechanisms driving lung tumorigenesis, aggressiveness, metastasization, and resistance to treatments could provide new tools for detecting the disease at an earlier stage and for a better response to therapy. In this scenario, Yes Associated Protein (YAP) and Trascriptional Coactivator with PDZ-binding motif (TAZ), the final effectors of the Hippo signaling transduction pathway, are emerging as promising therapeutic targets. Here, we will discuss the most recent advances made in YAP and TAZ biology in lung cancer and, more importantly, on the newly discovered mechanisms of YAP and TAZ inhibition in lung cancer as well as their clinical implications.

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YAP triggers the Wnt/β-catenin signalling pathway and promotes enterocyte self-renewal, regeneration and tumorigenesis after DSS-induced injury

Cited by 164 publications

References 47 publications

The Hippo Pathway: Immunity and Cancer

The Hippo Pathway: Immunity and Cancer

Regulatory Mechanisms of the Wnt/β-Catenin Pathway in Diabetic Cutaneous Ulcers

YAP and TAZ in Lung Cancer: Oncogenic Role and Clinical Targeting

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