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      Cancer stem cells as key drivers of tumour progression

      review-article

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          Abstract

          Background

          Cancer stem cells (CSCs) are subpopulations of cancer cells sharing similar characteristics as normal stem or progenitor cells such as self-renewal ability and multi-lineage differentiation to drive tumour growth and heterogeneity. Throughout the cancer progression, CSC can further be induced from differentiated cancer cells via the adaptation and cross-talks with the tumour microenvironment as well as a response from therapeutic pressures, therefore contributes to their heterogeneous phenotypes. Challengingly, conventional cancer treatments target the bulk of the tumour and are unable to target CSCs due to their highly resistance nature, leading to metastasis and tumour recurrence.

          Main body

          This review highlights the roles of CSCs in tumour initiation, progression and metastasis with a focus on the cellular and molecular regulators that influence their phenotypical changes and behaviours in the different stages of cancer progression. We delineate the cross-talks between CSCs with the tumour microenvironment that support their intrinsic properties including survival, stemness, quiescence and their cellular and molecular adaptation in response to therapeutic pressure. An insight into the distinct roles of CSCs in promoting angiogenesis and metastasis has been captured based on in vitro and in vivo evidences.

          Conclusion

          Given dynamic cellular events along the cancer progression and contributions of resistance nature by CSCs, understanding their molecular and cellular regulatory mechanism in a heterogeneous nature, provides significant cornerstone for the development of CSC-specific therapeutics.

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          Most cited references115

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          The metastatic niche: adapting the foreign soil.

          The 'seed and soil' hypothesis for metastasis sets forth the concept that a conducive microenvironment, or niche, is required for disseminating tumour cells to engraft distant sites. This Opinion presents emerging data that support this concept and outlines the potential mechanism and temporal sequence by which changes occur in tissues distant from the primary tumour. To enable improvements in the prognosis of advanced malignancy, early interventions that target both the disseminating seed and the metastatic soil are likely to be required.
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            Molecular regulation of stem cell quiescence.

            Subsets of mammalian adult stem cells reside in the quiescent state for prolonged periods of time. This state, which is reversible, has long been viewed as dormant and with minimal basal activity. Recent advances in adult stem cell isolation have provided insights into the epigenetic, transcriptional and post-transcriptional control of quiescence and suggest that quiescence is an actively maintained state in which signalling pathways are involved in maintaining a poised state that allows rapid activation. Deciphering the molecular mechanisms regulating adult stem cell quiescence will increase our understanding of tissue regeneration mechanisms and how they are dysregulated in pathological conditions and in ageing.
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              AACR centennial series: the biology of cancer metastasis: historical perspective.

              Metastasis resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His "seed and soil" hypothesis was substantiated a century later with experimental studies, and numerous reports have confirmed these seminal observations. An improved understanding of the metastatic process and the attributes of the cells selected by this process is critical for the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, so metastasis prevention may not be relevant. Treating systemic disease and identifying patients with early disease should be our goal. Revitalized research in the past three decades has focused on new discoveries in the biology of metastasis. Even though our understanding of molecular events that regulate metastasis has improved, the contributions and timing of molecular lesion(s) involved in metastasis pathogenesis remain unclear. Review of the history of pioneering observations and discussion of current controversies should increase understanding of the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and should lead to the design of successful therapy. (c)2010 AACR.
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                Author and article information

                Contributors
                azayob@um.edu.my
                +603 7967 4719 , selvee@ummc.edu.my
                Journal
                J Biomed Sci
                J. Biomed. Sci
                Journal of Biomedical Science
                BioMed Central (London )
                1021-7770
                1423-0127
                6 March 2018
                6 March 2018
                2018
                : 25
                : 20
                Affiliations
                [1 ]ISNI 0000 0001 2308 5949, GRID grid.10347.31, Stem Cell Biology Laboratory, Department of Molecular Medicine, Faculty of Medicine, , University of Malaya, ; 50603 Wilayah Persekutuan Kuala Lumpur, Malaysia
                [2 ]ISNI 0000 0001 2308 5949, GRID grid.10347.31, Cell and Molecular Laboratory (CMBL), The Dean’s Office, Faculty of Medicine, , University of Malaya, ; 50603 Wilayah Persekutuan Kuala Lumpur, Malaysia
                Article
                426
                10.1186/s12929-018-0426-4
                5838954
                29506506
                78a8682b-1827-4afd-84d7-69019654c334
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                History
                : 4 September 2017
                : 1 March 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004386, Universiti Malaya;
                Award ID: RP032-14HTM
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Molecular medicine
                cancer stem cells,resistance,stemness,tumour microenvironment,extracellular matrix,hypoxia,exosomes,quiescence,angiogenesis,metastasis

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