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Li L.,Beijing Institute of Radiation Medicine | Li W.,The Texas Institute | Li W.,University of Texas Health Science Center at Houston
Pharmacology and Therapeutics | Year: 2015

The epithelial-mesenchymal transition (EMT) is a developmental process that is important for embryogenesis, wound healing, organ fibrosis, and cancer metastasis. Cancer-associated EMT is not a simple process to acquire migration and invasion ability, but a complicated and comprehensive reprogramming, involved in metabolism, epigenetics and differentiation, through which differentiated epithelial cancer cells reverse to an undifferentiated state, not only expressing stem cell markers, but also acquiring stem cell-like functions. Here we review recent ideas and discoveries that illustrate the links among metabolism, epigenetics, and dedifferentiation during EMT, with special emphasis on the primary driving force and ultimate goal of cancer-associated EMT - of the energy and for the energy. Furthermore, we highlight on the specificity of epigenetic modification during EMT, with an aim to explain how the repression of epithelial genes and activation of mesenchymal genes are coordinated simultaneously through EMT. Finally, we provide an outlook on anti-EMT therapeutic approach on epigenetic and metabolic levels, and discuss its potential for clinical application. © 2015 Elsevier Inc. All rights reserved.


Cao Y.,Beijing Institute of Radiation Medicine | Zhang L.,Beijing Institute of Radiation Medicine | Zhang L.,Dalian Medical University
Cellular and Molecular Life Sciences | Year: 2013

Since being discovered and intensively studied for over a decade, Smad ubiquitylation regulatory factor-1 (Smurf1) has been linked with several important biological pathways, including the bone morphogenetic protein pathway, the non-canonical Wnt pathway, and the mitogen-activated protein kinase pathway. Multiple functions of this ubiquitin ligase have been discovered in cell growth and morphogenesis, cell migration, cell polarity, and autophagy. Smurf1 is related to physiological manifestations in terms of age-dependent deficiency in bone formation and invasion of tumor cells. Smurf1-knockout mice have a significant phenotype in the skeletal system and considerable manifestations during embryonic development and neural outgrowth. In depth studying of Smurf1 will help us to understand the etiopathological mechanisms of related disorders. Here, we will summarize historical and recent studies on Smurf1, and discuss the E3 ligase-dependent and -independent functions of Smurf1. Moreover, intracellular regulations of Smurf1 and related physiological phenotypes will be described in this review. © 2012 Springer Basel.


Shi Y.,Baylor College of Medicine | Xu P.,Beijing Institute of Radiation Medicine | Qin J.,Baylor College of Medicine
Molecular and Cellular Proteomics | Year: 2011

Ubiquitin (Ub) is a small and highly conserved protein that can covalently modify protein substrates. Ubiquitination is one of the major post-translational modifications that regulate a broad spectrum of cellular functions. The advancement of mass spectrometers as well as the development of new affinity purification tools has greatly expedited proteome-wide analysis of several post-translational modifications (e.g. phosphorylation, glycosylation, and acetylation). In contrast, large-scale profiling of lysine ubiquitination remains a challenge. Most recently, new Ub affinity reagents such as Ub remnant antibody and tandem Ub binding domains have been developed, allowing for relatively large-scale detection of several hundreds of lysine ubiquitination events in human cells. Here we review different strategies for the identification of ubiquitination site and discuss several issues associated with data analysis. We suggest that careful interpretation and orthogonal confirmation of MS spectra is necessary to minimize false positive assignments by automatic searching algorithms. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Yang L.,Beijing Institute of Radiation Medicine | Peng R.,Beijing Institute of Radiation Medicine
Stem Cell Reviews and Reports | Year: 2010

Adult mammalian skin consists of the epidermis, hair follicles (HFs), and sebaceous glands (SGs). Each of these three epithelial lineages contains its own stem cell (SC) population for normal tissue homeostasis, HF cycling, and repair of the epidermis following injury. Here, we provide an overview of the current knowledge on follicle SCs of the adult skin, including their essential features and, most importantly, the control of follicle SC fate. Wnt/β-catenin is required for follicle SC maintenance and niche biology, and β-catenin activation is essential for promoting quiescent follicle SCs to proliferate and terminally differentiate along the hair cell lineage. Further, β-catenin stabilization promotes de novo HF morphogenesis, and constitutively active β-catenin expression results in pilomatricoma. Both bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) signals are required for quiescent niche maintenance: BMP deletion results in SC activation, whereas TGF-β may play a role in SC identity maintenance. © 2010 Springer Science+Business Media, LLC.


Li P.Y.,Beijing Institute of Radiation Medicine
Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji | Year: 2011

microRNAs (miRNAs) are a highly conserved class of small noncoding RNAs that regulate gene expression by post-transcriptional degradation or translational repression. miRNAs are involved in the regulation of cell apoptosis, proliferation, differentiation and other physiological processes, and are closely related with the development of cancer. More recently, it has been proposed that the presence of genetic variations (e.g., single nucleotide polymorphism and copy number variation) in microRNA genes, their biogenesis pathway and target binding sites affect the miRNA processing machinery and targeting, and have a significant genetic effect. In this review, we focus on the miRNA-related genetic variations and cancer susceptibility and progression.

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