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      The lipid rafts in cancer stem cell: a target to eradicate cancer

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          Abstract

          Cancer stem cells (CSCs) are a subpopulation of cancer cells with stem cell properties that sustain cancers, which may be responsible for cancer metastasis or recurrence. Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in the plasma membrane that mediate various intracellular signaling. The occurrence and progression of cancer are closely related to lipid rafts. Emerging evidence indicates that lipid raft levels are significantly enriched in CSCs compared to cancer cells and that most CSC markers such as CD24, CD44, and CD133 are located in lipid rafts. Furthermore, lipid rafts play an essential role in CSCs, specifically in CSC self-renewal, epithelial-mesenchymal transition, drug resistance, and CSC niche. Therefore, lipid rafts are critical regulatory platforms for CSCs and promising therapeutic targets for cancer therapy.

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          Hallmarks of Cancer: New Dimensions

          The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
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            A framework for advancing our understanding of cancer-associated fibroblasts

            Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.
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              The senescence-associated secretory phenotype: the dark side of tumor suppression.

              Cellular senescence is a tumor-suppressive mechanism that permanently arrests cells at risk for malignant transformation. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression.
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                Author and article information

                Contributors
                lqin@hnucm.edu.cn
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                30 August 2022
                30 August 2022
                2022
                : 13
                : 432
                Affiliations
                [1 ]GRID grid.488482.a, ISNI 0000 0004 1765 5169, Laboratory of Stem Cell Regulation With Chinese Medicine and Its Application, School of Pharmacy, , Hunan University of Chinese Medicine, ; 300 Xueshi Road, Hanpu Science and Education District, 410208 Changsha, Hunan People’s Republic of China
                [2 ]GRID grid.488482.a, ISNI 0000 0004 1765 5169, Department of Urology, , The First Hospital of Hunan University of Chinese Medicine, ; Changsha, China
                [3 ]GRID grid.488482.a, ISNI 0000 0004 1765 5169, Institutional Key Laboratory of Vascular Biology and Translational Medicine in Hunan Province, , Hunan University of Chinese Medicine, ; Changsha, China
                [4 ]GRID grid.488482.a, ISNI 0000 0004 1765 5169, Hunan Province Engineering Research Center of Bioactive Substance Discovery of Traditional Chinese Medicine, , Hunan University of Chinese Medicine, ; Changsha, China
                Author information
                http://orcid.org/0000-0002-9797-2636
                Article
                3111
                10.1186/s13287-022-03111-8
                9429646
                36042526
                392a37dd-deea-4e08-9489-870392e6f8a3
                © The Author(s) 2022

                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
                : 18 May 2022
                : 3 August 2022
                Funding
                Funded by: the National Natural Sciences Foundation of China
                Award ID: 81973668
                Award Recipient :
                Funded by: the National Natural Sciences Foundation of China
                Award ID: 81774130
                Award Recipient :
                Funded by: the Key Project of the Educational Department of Hunan Province
                Award ID: 20A375
                Award Recipient :
                Funded by: Pharmaceutical Open Fund of Domestic First-class Disciplines (cultivation) of Hunan Province
                Award ID: 2021YX07
                Award Recipient :
                Funded by: the Scientific Research Project of Changsha Science and Technology Bureau
                Award ID: kq2004060
                Award Recipient :
                Funded by: Key Project of Hunan Provincial Health Commission
                Award ID: 202213055529
                Award Recipient :
                Funded by: the Graduate Research innovation project of Hunan University of Chinese Medicine
                Award ID: 2021CX48
                Award ID: 2021CX08
                Award Recipient :
                Funded by: the First-Class Discipline of Pharmaceutical Science of Hunan
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2022JJ80088
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Molecular medicine
                lipid raft,cancer,cancer stem cell,self-renewal,drug resistance,epithelial-mesenchymal transition,cancer stem cell niche

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