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Yao Chen

Bio: Yao Chen is an academic researcher from Second Military Medical University. The author has contributed to research in topics: Gankyrin & Tumor progression. The author has an hindex of 17, co-authored 25 publications receiving 960 citations.

Papers
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Journal ArticleDOI
TL;DR: Given the efficacy of ADRB2 modulation on HCC inhibition and sorafenib resistance, adrenoceptor antagonist appears to be a putative novel treatment for HCC and chemoresistance.

134 citations

Journal ArticleDOI
TL;DR: It is reported that increased expression of p28GANK (Gankyrin, PSMD10, or p28) in human HCC predicts poor survival and disease recurrence after surgery, and the combination of these two parameters is a more powerful predictor of poor prognosis.

119 citations

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TL;DR: OV6(+) HCC cells may represent a subpopulation of T-ICs with augmented invasion and metastatic potential, which contribute to progression and metastasis of HCC.

111 citations

Journal ArticleDOI
TL;DR: It is reported that PSMD10/gankyrin promotes autophagy in hepatocellular carcinoma (HCC) in response to starvation or stress through 2 complementary routes, and this results present a novel mechanism involving modulation of ATG7 by PS MD10 in sustainingAutophagy, promoting HCC cell survival against starvation or chemotherapy.
Abstract: Although autophagy is most critical for survival of cancer cells, especially in fast-growing tumors, the mechanism remains to be fully characterized Herein we report that PSMD10/gankyrin promotes autophagy in hepatocellular carcinoma (HCC) in response to starvation or stress through 2 complementary routes PSMD10 was physically associated with ATG7 in the cytoplasm, and this association was enhanced by initial nutrient deprivation Subsequently, PSMD10 translocated into the nucleus and bound cooperatively with nuclear HSF1 (heat shock transcription factor 1) onto the ATG7 promoter, upregulated ATG7 expression in the advanced stage of starvation Intriguingly, the type of PSMD10-mediated autophagy was independent of the proteasome system, although PSMD10 has been believed to be an indispensable chaperone for assembly of the 26S proteasome A significant correlation between PSMD10 expression and ATG7 levels was detected in human HCC biopsies, and the combination of these 2 parameters is a powerful

106 citations

Journal ArticleDOI
TL;DR: Elevated cyclin G1 facilitates HCC metastasis by promoting EMT via PI3K/Akt/GSK‐3β/Snail‐dependent pathway and may serve as a novel prognostic biomarker and therapeutic target.

97 citations


Cited by
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Journal ArticleDOI
TL;DR: The mechanism of autophagy under stressful conditions and its roles in tumor suppression and promotion in cancer and in cancer stem-cells are summarized and how Autophagy is a promising potential therapeutic target in cancer treatment is discussed.
Abstract: Autophagy is an intracellular degradative process that occurs under several stressful conditions, including organelle damage, the presence of abnormal proteins, and nutrient deprivation. The mechanism of autophagy initiates the formation of autophagosomes that capture degraded components and then fuse with lysosomes to recycle these components. The modulation of autophagy plays dual roles in tumor suppression and promotion in many cancers. In addition, autophagy regulates the properties of cancer stem-cells by contributing to the maintenance of stemness, the induction of recurrence, and the development of resistance to anticancer reagents. Although some autophagy modulators, such as rapamycin and chloroquine, are used to regulate autophagy in anticancer therapy, since this process also plays roles in both tumor suppression and promotion, the precise mechanism of autophagy in cancer requires further study. In this review, we will summarize the mechanism of autophagy under stressful conditions and its roles in tumor suppression and promotion in cancer and in cancer stem-cells. Furthermore, we discuss how autophagy is a promising potential therapeutic target in cancer treatment.

541 citations

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TL;DR: This review summarizes the current understanding of the key role of miR-122 in liver physiology and disease and discusses the perspectives of miRNA-based therapeutic approaches for viral hepatitis and liver disease.

476 citations

Journal ArticleDOI
TL;DR: It is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems, especially for HCC patients.
Abstract: Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma (HCC) in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies have revealed that in addition to the primary resistance, several mechanisms are underlying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients.

442 citations

Journal ArticleDOI
TL;DR: An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies.
Abstract: Liver cancer is an aggressive disease with a poor outcome. Several hepatic stem/progenitor markers are useful for isolating a subset of liver cells with stem cell features, known as cancer stem cells (CSCs). These cells are responsible for tumor relapse, metastasis, and chemoresistance. Liver CSCs dictate a hierarchical organization that is shared in both organogenesis and tumorigenesis. An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies. This Review highlights recent advances in understanding the pathogenesis of liver CSCs and discusses unanswered questions about the concept of liver CSCs.

432 citations

Journal ArticleDOI
TL;DR: This review will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors, and how this pivotal kinase interacts with multiple signaling pathways.
Abstract: // James A. McCubrey 1 , Linda S. Steelman 1 , Fred E. Bertrand 2 , Nicole M. Davis 1 , Melissa Sokolosky 1 , Steve L. Abrams 1 , Giuseppe Montalto 3 , Antonino B. D’Assoro 4 , Massimo Libra 5 , Ferdinando Nicoletti 5 , Roberta Maestro 6 , Jorg Basecke 7,8 , Dariusz Rakus 9 , Agnieszka Gizak 9 Zoya Demidenko 10 , Lucio Cocco 11 , Alberto M. Martelli 11 and Melchiorre Cervello 12 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC, USA 2 Department of Oncology, Brody School of Medicine at East Carolina University Greenville, NC, USA 3 Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy 4 Department of Medical Oncology, Mayo Clinic Cancer Center, Rochester, MN, USA 5 Department of Bio-Medical Sciences, University of Catania, Catania, Italy 6 Experimental Oncology 1, CRO IRCCS, National Cancer Institute, Aviano, Pordenone, Italy. 7 Department of Medicine, University of Gottingen, Gottingen, Germany 8 Sanct-Josef-Hospital Cloppenburg, Department of Hematology and Oncology, Cloppenburg, Germany 9 Department of Animal Molecular Physiology, Institute of Experimental Biology, Wroclaw University, Wroclaw, Poland 10 Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA 11 Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy 12 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy Correspondence: James A. McCubrey, email: // Keywords : GSK-3, cancer stem cells, Wnt/beta-catenin, PI3K, Akt, mTOR, Hedgehog, Notch, Targeted Therapy, Therapy Resistance, Mutations, Rapamycin Received : April 24, 2014 Accepted : May 28, 2014 Published : May 28, 2014 Abstract The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer’s disease, Parkinson’s disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.

413 citations