title: Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a "Watch-and-Wait" Approach to Cancer.
abstract: BACKGROUND
  Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific manner.
  
  
  OBJECTIVE
  Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a "watchand- wait" approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology - a balance that needs to be maintained for the "watch-and-wait" approach to cancer.
  
  
  CONCLUSIONS
  This review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application.
authors.affiliation: Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children's Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, United States.
authors.forename: Shengwen Calvin
authors.initials: SC
authors.lastname: Li
authors.affiliation: Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children's Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, United States.
authors.forename: Long T
authors.initials: LT
authors.lastname: Vu
authors.affiliation: AB Sciex, Inc., 250 S. Kraemer Blvd., Brea, CA 92822, United States.
authors.forename: Jane Jianying
authors.initials: JJ
authors.lastname: Luo
authors.affiliation: Division of Periodontology, Diagnostic Sciences & Dental Hygiene and Biomedical Sciences, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, United States.
authors.forename: Jiang F
authors.initials: JF
authors.lastname: Zhong
authors.affiliation: Division of Periodontology, Diagnostic Sciences & Dental Hygiene and Biomedical Sciences, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, United States.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children's Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, United States.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Dethlefs
authors.affiliation: Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children's Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, United States.
authors.forename: William G
authors.initials: WG
authors.lastname: Loudon
authors.affiliation: Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children's Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, United States.
authors.forename: Mustafa H
authors.initials: MH
authors.lastname: Kabeer
mesh_terms: D000818:Animals; D004548:Elasticity / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: Tissue elasticity; cancer stem cells; gene expression; miRNAs; stem cell biology; tumor microenvironment