scholarly journals YAP/Hippo Pathway and Cancer Immunity: It Takes Two to Tango

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1949
Author(s):  
Dimitrios Matthaios ◽  
Maria Tolia ◽  
Davide Mauri ◽  
Konstantinos Kamposioras ◽  
Michalis Karamouzis
Keyword(s):  
Tissue Regeneration ◽  
Hippo Pathway ◽  
Treatment Strategies ◽  
Suppressor Cells ◽  
Tissue Homeostasis ◽  
Myeloid Derived Suppressor Cells ◽  
Cancer Immunity ◽  
Healing Tissue ◽  
The Hippo Pathway ◽  
Egfr Tki

Hippo pathway with its main molecule YAP is a crucial pathway for development, tissue homeostasis, wound healing, tissue regeneration, and cancer. In this review, we discuss the multiple effects of the YAP/Hippo pathway in the immune system and cancer. We analyzed a series of effects: extracellular vesicles enhanced immunity through inhibition of LATS1/2, ways of modulation of the tumor microenvironment, YAP- and TAZ-mediated upregulation of PDL1, high expression of YAP and PDL1 in EGFR-TKI-resistant cells, enhanced YAP activity in inflammation, and the effect of the Hippo pathway on T cells, B cells, Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs). These pleiotropic effects render the YAP and Hippo pathway a key pathway for exploitation in the future, in order to enhance our immunotherapy treatment strategies in oncology.

scholarly journals The Hippo pathway and cancer immunity: Friend or foe?

Oncoscience ◽  
2018 ◽  
Vol 5 (3-4) ◽  
pp. 49-50 ◽  
Author(s):  
Helena J. Janse van Rensburg ◽  
Xiaolong Yang
Keyword(s):  
Hippo Pathway ◽  
Cancer Immunity ◽  
The Hippo Pathway

scholarly journals The Hippo Pathway: Immunity and Cancer

Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 94 ◽  
Author(s):  
Zaid Taha ◽  
Helena Janse van Rensburg ◽  
Xiaolong Yang
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mammalian Cells ◽  
Immune Cell ◽  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
Hippo Signaling ◽  
Core Components ◽  
The Hippo Pathway ◽  
Future Work

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.

scholarly journals Loss of Two-Pore Channel 2 (TPC2) Expression Increases the Metastatic Traits of Melanoma Cells by a Mechanism Involving the Hippo Signalling Pathway and Store-Operated Calcium Entry

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2391 ◽  
Author(s):  
Antonella D’Amore ◽  
Ali Ahmed Hanbashi ◽  
Silvia Di Agostino ◽  
Fioretta Palombi ◽  
Andrea Sacconi ◽  
...  
Keyword(s):  
Target Genes ◽  
Hippo Pathway ◽  
Treatment Strategies ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Pore Channel ◽  
Cancer Aggressiveness ◽  
Store Operated Calcium Entry ◽  
Enhanced Secretion ◽  
The Hippo Pathway

Melanoma is one of the most aggressive and treatment-resistant human cancers. The two-pore channel 2 (TPC2) is located on late endosomes, lysosomes and melanosomes. Here, we characterized how TPC2 knockout (KO) affected human melanoma cells derived from a metastatic site. TPC2 KO increased these cells’ ability to invade the extracelullar matrix and was associated with the increased expression of mesenchymal markers ZEB-1, Vimentin and N-Cadherin, and the enhanced secretion of MMP9. TPC2 KO also activated genes regulated by YAP/TAZ, which are key regulators of tumourigenesis and metastasis. Expression levels of ORAI1, a component of store-operated Ca2+ entry (SOCE), and PKC-βII, part of the HIPPO pathway that negatively regulates YAP/TAZ activity, were reduced by TPC2 KO and RNA interference knockdown. We propose a cellular mechanism mediated by ORAI1/Ca2+/PKC-βII to explain these findings. Highlighting their potential clinical significance, patients with metastatic tumours showed a reduction in TPC2 expression. Our research indicates a novel role of TPC2 in melanoma. While TPC2 loss may not activate YAP/TAZ target genes in primary melanoma, in metastatic melanoma it could activate such genes and increase cancer aggressiveness. These findings aid the understanding of tumourigenesis mechanisms and could provide new diagnostic and treatment strategies for skin cancer and other metastatic cancers.

scholarly journals Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Hiroshi Katoh ◽  
Masahiko Watanabe
Keyword(s):  
T Cells ◽  
Cancer Progression ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Suppressor Cells ◽  
Response To Treatment ◽  
Solid Cancer ◽  
Myeloid Derived Suppressor Cells ◽  
Immune Cell Population ◽  
Novel Treatment Strategies

Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs). Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

The Sterile 20-Like Kinase Tao Controls Tissue Homeostasis by Regulating the Hippo Pathway in Drosophila Adult Midgut

2014 ◽  
Vol 41 (8) ◽  
pp. 429-438 ◽  
Author(s):  
Xudong Huang ◽  
Lai Shi ◽  
Jun Cao ◽  
Fangfei He ◽  
Renling Li ◽  
...  
Keyword(s):  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
The Hippo Pathway

scholarly journals Hippo and rassf1a Pathways: A Growing Affair

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Francesca Fausti ◽  
Silvia Di Agostino ◽  
Andrea Sacconi ◽  
Sabrina Strano ◽  
Giovanni Blandino
Keyword(s):  
Developmental Biology ◽  
Tissue Regeneration ◽  
Target Genes ◽  
Hippo Pathway ◽  
Hippo Signaling ◽  
Transcriptional Coactivator ◽  
Pathway Activity ◽  
Kinase Cascade ◽  
The Hippo Pathway ◽  
The Impact

First discovered in Drosophila, the Hippo pathway regulates the size and shape of organ development. Its discovery and study have helped to address longstanding questions in developmental biology. Central to this pathway is a kinase cascade leading from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the Yki protein (YAP and TAZ in mammals), a transcriptional coactivator of target genes involved in cell proliferation, survival, and apoptosis. A dysfunction of the Hippo pathway activity is frequently detected in human cancers. Recent studies have highlighted that the Hippo pathway may play an important role in tissue homoeostasis through the regulation of stem cells, cell differentiation, and tissue regeneration. Recently, the impact of RASSF proteins on Hippo signaling potentiating its proapoptotic activity has been addressed, thus, providing further evidence for Hippo's key role in mammalian tumorigenesis as well as other important diseases.

scholarly journals Mutations and Copy Number Abnormalities of Hippo Pathway Components in Human Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhengjin He ◽  
Ruihan Li ◽  
Hai Jiang
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Copy Number ◽  
Human Cancer ◽  
Hippo Pathway ◽  
Copy Number Variations ◽  
Tissue Homeostasis ◽  
Hippo Signaling ◽  
Core Components ◽  
The Hippo Pathway

The Hippo pathway is highly conserved from Drosophila to mammals. As a key regulator of cell proliferation, the Hippo pathway controls tissue homeostasis and has a major impact on tumorigenesis. The originally defined core components of the Hippo pathway in mammals include STK3/4, LATS1/2, YAP1/TAZ, TEAD, VGLL4, and NF2. However, for most of these genes, mutations and copy number variations are relatively uncommon in human cancer. Several other recently identified upstream and downstream regulators of Hippo signaling, including FAT1, SHANK2, Gq/11, and SWI/SNF complex, are more commonly dysregulated in human cancer at the genomic level. This review will discuss major genomic events in human cancer that enable cancer cells to escape the tumor-suppressive effects of Hippo signaling.

scholarly journals The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity

Cell ◽  
2016 ◽  
Vol 167 (6) ◽  
pp. 1525-1539.e17 ◽  
Author(s):  
Toshiro Moroishi ◽  
Tomoko Hayashi ◽  
Wei-Wei Pan ◽  
Yu Fujita ◽  
Matthew V. Holt ◽  
...  
Keyword(s):  
Hippo Pathway ◽  
Cancer Immunity ◽  
The Hippo Pathway

scholarly journals Regulation and functions of the Hippo pathway in stemness and differentiation

2020 ◽  
Vol 52 (7) ◽  
pp. 736-748 ◽  
Author(s):  
Xiaolei Cao ◽  
Chenliang Wang ◽  
Jiyang Liu ◽  
Bin Zhao
Keyword(s):  
Cell Proliferation ◽  
Tissue Regeneration ◽  
Hippo Pathway ◽  
Binding Motif ◽  
Cell Fates ◽  
Self Renewal ◽  
Proliferation And Apoptosis ◽  
Kinase Cascade ◽  
The Hippo Pathway

Abstract The Hippo pathway plays important roles in organ development, tissue regeneration, and human diseases, such as cancer. In the canonical Hippo pathway, the MST1/2-LATS1/2 kinase cascade phosphorylates and inhibits transcription coactivators Yes-associated protein and transcription coactivator with PDZ-binding motif and thus regulates transcription of genes important for cell proliferation and apoptosis. However, recent studies have depicted a much more complicate picture of the Hippo pathway with many new components and regulatory stimuli involving both chemical and mechanical signals. Furthermore, accumulating evidence indicates that the Hippo pathway also plays important roles in the determination of cell fates, such as self-renewal and differentiation. Here, we review regulations of the Hippo pathway and its functions in stemness and differentiation emphasizing recent discoveries.

scholarly journals Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kai Li ◽  
Houhui Shi ◽  
Benxia Zhang ◽  
Xuejin Ou ◽  
Qizhi Ma ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Immune Escape ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Suppressor Cells ◽  
Preclinical Studies ◽  
Myeloid Derived Suppressor Cells ◽  
New Ideas ◽  
Immature Myeloid Cells ◽  
Therapy Treatment

AbstractMyeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid cells with immunosuppressive effects, which undergo massive expansion during tumor progression. These cells not only support immune escape directly but also promote tumor invasion via various non-immunological activities. Besides, this group of cells are proved to impair the efficiency of current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs are considered as potential therapeutic targets for cancer therapy. Treatment strategies targeting MDSCs have shown promising outcomes in both preclinical studies and clinical trials when administrated alone, or in combination with other anticancer therapies. In this review, we shed new light on recent advances in the biological characteristics and immunosuppressive functions of MDSCs. We also hope to propose an overview of current MDSCs-targeting therapies so as to provide new ideas for cancer treatment.

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