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      The Hippo signaling pathway in leukemia: function, interaction, and carcinogenesis

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          Abstract

          Cancer can be considered as a communication disease between and within cells; nevertheless, there is no effective therapy for the condition, and this disease is typically identified at its late stage. Chemotherapy, radiation, and molecular-targeted treatment are typically ineffective against cancer cells. A better grasp of the processes of carcinogenesis, aggressiveness, metastasis, treatment resistance, detection of the illness at an earlier stage, and obtaining a better therapeutic response will be made possible. Researchers have discovered that cancerous mutations mainly affect signaling pathways. The Hippo pathway, as one of the main signaling pathways of a cell, has a unique ability to cause cancer. In order to treat cancer, a complete understanding of the Hippo signaling system will be required. On the other hand, interaction with other pathways like Wnt, TGF-β, AMPK, Notch, JNK, mTOR, and Ras/MAP kinase pathways can contribute to carcinogenesis. Phosphorylation of oncogene YAP and TAZ could lead to leukemogenesis, which this process could be regulated via other signaling pathways. This review article aimed to shed light on how the Hippo pathway interacts with other cellular signaling networks and its functions in leukemia.

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          Most cited references108

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          Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer.

          Two decades of studies in multiple model organisms have established the Hippo pathway as a key regulator of organ size and tissue homeostasis. By inhibiting YAP and TAZ transcription co-activators, the Hippo pathway regulates cell proliferation, apoptosis, and stemness in response to a wide range of extracellular and intracellular signals, including cell-cell contact, cell polarity, mechanical cues, ligands of G-protein-coupled receptors, and cellular energy status. Dysregulation of the Hippo pathway exerts a significant impact on cancer development. Further investigation of the functions and regulatory mechanisms of this pathway will help uncovering the mystery of organ size control and identify new targets for cancer treatment.
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            The Hippo Pathway: Biology and Pathophysiology

            The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size control, and regeneration. The core of the Hippo pathway in mammals consists of a kinase cascade, MST1/2 and LATS1/2, as well as downstream effectors, transcriptional coactivators YAP and TAZ. These core components of the Hippo pathway control transcriptional programs involved in cell proliferation, survival, mobility, stemness, and differentiation. The Hippo pathway is tightly regulated by both intrinsic and extrinsic signals, such as mechanical force, cell–cell contact, polarity, energy status, stress, and many diffusible hormonal factors, the majority of which act through G protein–coupled receptors. Here, we review the current understanding of molecular mechanisms by which signals regulate the Hippo pathway with an emphasis on mechanotransduction and the effects of this pathway on basic biology and human diseases.
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              YAP/TAZ upstream signals and downstream responses

              Cell behavior is strongly influenced by physical, mechanical contacts between cells and their extracellular matrix. We review how the transcriptional regulators YAP/TAZ integrate mechanical cues with the response to soluble signals and metabolic pathways to control multiple aspects of cell behavior, including proliferation, cell plasticity and stemness essential for tissue regeneration. Corruption of cell-environment interplay leads to aberrant YAP/TAZ activation that is instrumental for multiple diseases, including cancer.
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                Author and article information

                Contributors
                Kavianpour.maria@gmail.com
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                25 December 2021
                25 December 2021
                2021
                : 21
                : 705
                Affiliations
                [1 ]Behbahan Faculty of Medical Sciences, Behbahan, Iran
                [2 ]GRID grid.411036.1, ISNI 0000 0001 1498 685X, Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, , Isfahan University of Medical Sciences, ; Isfahan, Iran
                [3 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Gene Therapy Research Center, Digestive Diseases Research Institute, , Tehran University of Medical Sciences, ; Tehran, Iran
                [4 ]GRID grid.412266.5, ISNI 0000 0001 1781 3962, Applied Cell Sciences and Hematology Department, Faculty of Medical Sciences, , Tarbiat Modares University, ; Tehran, Iran
                [5 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
                Author information
                http://orcid.org/0000-0002-8047-8754
                Article
                2408
                10.1186/s12935-021-02408-7
                8710012
                34953494
                e1128ceb-8531-4ae2-a66d-e2f42e1eb897
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 24 August 2021
                : 13 December 2021
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                hippo signaling pathway,signaling,leukemia,hematologic neoplasms,cancer
                Oncology & Radiotherapy
                hippo signaling pathway, signaling, leukemia, hematologic neoplasms, cancer

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