RACK1 Promotes Self-Renewal and Chemoresistance of Cancer Stem Cells in Human Hepatocellular Carcinoma through Stabilizing Nanog.

Abstract:

:Targeting cancer stem cells (CSCs) has been proposed as a new strategy to eradicate malignancies, including hepatocellular carcinoma (HCC). However, the mechanisms by which CSCs sustain their self-renewal and chemoresistance remain elusive. Nanog is a master transcriptional regulator of stemness, especially in CSCs. Its expression is tightly regulated by the ubiquitin-proteasome system in embryonic stem cells (ESCs). Whether the suppression of Nanog ubiquitination contributes to its over-expression in CSCs has not been explored. In addition, the role of receptor for activated C kinase 1 (RACK1), an adaptor protein implicated in HCC growth, in liver CSC-like traits remains to be determined. Methods: In vitro and in vivo assays were performed to investigate the role of RACK1 in liver CSC-like phenotype and murine ESC function. How RACK1 regulates Nanog expression was explored by immunoblotting and immunohistochemistry. The interaction of RACK1 with Nanog and the consequent effects on Nanog ubiquitination and stemness were then analyzed. Results: RACK1 promotes self-renewal and chemoresistance of human liver CSCs and maintains murine ESC function. Consistently, RACK1 enhances the expression of Nanog in human HCC cells and murine ESCs. The protein levels of RACK1 in clinical HCC tissues positively correlate with those of Nanog. Further exploration indicates that RACK1 directly binds to Nanog, which prevents its recruitment of E3 ubiquitin ligase FBXW8 and ubiquitin-dependent degradation. The interaction with Nanog is essential for RACK1 to promote stemness. Conclusions: Our data provide novel insights into the regulation of Nanog protein levels, as well the key role of RACK1 to enhance self-renewal and chemoresistance of CSCs in human HCC.

journal_name

Theranostics

journal_title

Theranostics

authors

Cao J,Zhao M,Liu J,Zhang X,Pei Y,Wang J,Yang X,Shen B,Zhang J

doi

10.7150/thno.29271

subject

Has Abstract

pub_date

2019-01-24 00:00:00

pages

811-828

issue

3

issn

1838-7640

pii

thnov09p0811

journal_volume

9

pub_type

杂志文章
  • pH responsive superporogen combined with PDT based on poly Ce6 ionic liquid grafted on SiO2 for combating MRSA biofilm infection.

    abstract::Background: Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. M...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.42922

    authors: Wang C,Chen P,Qiao Y,Kang Y,Yan C,Yu Z,Wang J,He X,Wu H

    更新日期:2020-03-26 00:00:00

  • Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells.

    abstract::Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)wo...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.10804

    authors: Shen H,Shi S,Zhang Z,Gong T,Sun X

    更新日期:2015-04-05 00:00:00

  • VEGFC acts as a double-edged sword in renal cell carcinoma aggressiveness.

    abstract::Hypoxic zones are common features of metastatic tumors. Due to inactivation of the von Hippel-Lindau gene (VHL), renal cell carcinomas (RCC) show constitutive stabilization of the alpha subunit of the hypoxia-inducible factor (HIF). Thus, RCC represents a model of chronic hypoxia. Development of the lymphatic network ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.27794

    authors: Ndiaye PD,Dufies M,Giuliano S,Douguet L,Grépin R,Durivault J,Lenormand P,Glisse N,Mintcheva J,Vouret-Craviari V,Mograbi B,Wurmser M,Ambrosetti D,Rioux-Leclercq N,Maire P,Pagès G

    更新日期:2019-01-21 00:00:00

  • Agonist c-Met Monoclonal Antibody Augments the Proliferation of hiPSC-derived Hepatocyte-Like Cells and Improves Cell Transplantation Therapy for Liver Failure in Mice.

    abstract::Rationale: Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSCs) have been developed to address the shortage of primary human hepatocytes (PHHs) for therapeutic applications. However, the in vivo repopulation capacity of HLCs remains limited. This study investigated the roles of agoni...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.30009

    authors: Yuan L,Zhang Y,Liu X,Chen Y,Zhang L,Cao J,Li X,Wang M,Wu K,Zhang J,Liu G,Tang Q,Yuan Q,Cheng T,Xia N

    更新日期:2019-04-06 00:00:00

  • Endothelial cells produce angiocrine factors to regulate bone and cartilage via versatile mechanisms.

    abstract::Blood vessels are conduits distributed throughout the body, supporting tissue growth and homeostasis by the transport of cells, oxygen and nutrients. Endothelial cells (ECs) form the linings of the blood vessels, and together with pericytes, are essential for organ development and tissue homeostasis through producing ...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.45422

    authors: Zhu S,Bennett S,Kuek V,Xiang C,Xu H,Rosen V,Xu J

    更新日期:2020-05-01 00:00:00

  • MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3.

    abstract::Histone deacetylase 3 (HDAC3) plays a pivotal role in the repression of cartilage-specific gene expression in human chondrocytes. The aim of this study was to determine whether microRNA-193b-3p (miR-193b-3p) regulates the expression of HDAC3 during chondrogenesis and chondrocyte metabolism. Methods: miR-193b-3p expres...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.23547

    authors: Meng F,Li Z,Zhang Z,Yang Z,Kang Y,Zhao X,Long D,Hu S,Gu M,He S,Wu P,Chang Z,He A,Liao W

    更新日期:2018-04-15 00:00:00

  • Erratum: Twist promotes tumor metastasis in basal-like breast cancer by transcriptionally upregulating ROR1: Erratum.

    abstract::[This corrects the article DOI: 10.7150/thno.21477.]. ...

    journal_title:Theranostics

    pub_type: 已发布勘误

    doi:10.7150/thno.56462

    authors: Cao J,Wang X,Dai T,Wu Y,Zhang M,Cao R,Zhang R,Wang G,Jiang R,Zhou BP,Shi J,Kang T

    更新日期:2021-01-01 00:00:00

  • Noninvasive application of mesenchymal stem cell spheres derived from hESC accelerates wound healing in a CXCL12-CXCR4 axis-dependent manner.

    abstract::Mesenchymal stem cells (MSC) derived from adult tissues effectively promote wound healing. However, MSC quality varies, and the quantity of MSC is limited, as MSC are acquired through donations. Moreover, the survival and functioning of dissociated MSC delivered to an inflammatory lesion are subject to challenges. Met...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.32982

    authors: Wang X,Jiang B,Sun H,Zheng D,Zhang Z,Yan L,Li E,Wu Y,Xu RH

    更新日期:2019-08-14 00:00:00

  • Optogenetic control of mesenchymal cell fate towards precise bone regeneration.

    abstract::Rationale: Spatial-temporal control of cell fate in vivo is of great importance for regenerative medicine. Currently, there remain no practical strategies to tune cell-fate spatial-temporally. Optogenetics is a biological technique that widely used to control cell activity in genetically defined neurons in a spatiotem...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.36455

    authors: Wang W,Huang D,Ren J,Li R,Feng Z,Guan C,Bao B,Cai B,Ling J,Zhou C

    更新日期:2019-10-18 00:00:00

  • Lung Cancer-Targeting Peptides with Multi-subtype Indication for Combinational Drug Delivery and Molecular Imaging.

    abstract::Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.17573

    authors: Chi YH,Hsiao JK,Lin MH,Chang C,Lan CH,Wu HC

    更新日期:2017-04-10 00:00:00

  • Innate immunity derived factors as external modulators of the CXCL12-CXCR4 axis and their role in stem cell homing and mobilization.

    abstract::The α-chemokine CXCL12 (stromal derived factor-1; SDF-1) and its corresponding G(αI) protein-coupled CXCR4 receptor axis play an important role in retention of hematopoietic stem progenitor cells (HSPCs) in bone marrow (BM) stem cell niches. CXCL12 has also been identified as a strong chemoattractant for HSPCs and imp...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.4621

    authors: Ratajczak MZ,Serwin K,Schneider G

    更新日期:2013-01-01 00:00:00

  • CD146-targeted immunoPET and NIRF Imaging of Hepatocellular Carcinoma with a Dual-Labeled Monoclonal Antibody.

    abstract::Overexpression of CD146 has been correlated with aggressiveness, recurrence rate, and poor overall survival in hepatocellular carcinoma (HCC) patients. In this study, we set out to develop a CD146-targeting probe for high-contrast noninvasive in vivo positron emission tomography (PET) and near-infrared fluorescence (N...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.15568

    authors: Hernandez R,Sun H,England CG,Valdovinos HF,Ehlerding EB,Barnhart TE,Yang Y,Cai W

    更新日期:2016-08-08 00:00:00

  • Image guided biodistribution of drugs and drug delivery.

    abstract::Image guided technique is playing an increasingly important role in the investigation of the biodistribution and pharmacokinetics of drugs or drug delivery systems. The application of these new materials and techniques with combined properties of diagnosis and therapy can benefit the development of targeted drug deliv...

    journal_title:Theranostics

    pub_type: 社论

    doi:10.7150/thno.5321

    authors: Ding H,Wu F

    更新日期:2012-01-01 00:00:00

  • Diagnostic Accuracy of Ga-68-HBED-CC-PSMA-Ligand-PET/CT before Salvage Lymph Node Dissection for Recurrent Prostate Cancer.

    abstract::Background: By targeting the prostate-specific membrane antigen (PSMA) on prostate cancer (PCa) cells PSMA-PET/CT shows great potential in locating the site of biochemical recurrence even at low PSA (Prostate-specific antigen)-levels. Accurate imaging of PCa recurrent lymph node metastases (LNM) is crucial for metasta...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.18421

    authors: Jilg CA,Drendel V,Rischke HC,Beck T,Vach W,Schaal K,Wetterauer U,Schultze-Seemann W,Meyer PT

    更新日期:2017-04-10 00:00:00

  • Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody.

    abstract::Inadequate diagnostic methods for prostate cancer lead to over- and undertreatment, and the inability to intraoperatively visualize positive margins may limit the success of surgical resection. Prostate cancer visualization could be improved by combining the complementary modalities of immuno-positron emission tomogra...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.27679

    authors: Tsai WK,Zettlitz KA,Tavaré R,Kobayashi N,Reiter RE,Wu AM

    更新日期:2018-11-12 00:00:00

  • Acidic Microenvironment Up-Regulates Exosomal miR-21 and miR-10b in Early-Stage Hepatocellular Carcinoma to Promote Cancer Cell Proliferation and Metastasis.

    abstract::Rationale: The incidence of hepatocellular carcinoma is rising worldwide. It is predicted that nearly half of the early-stage hepatocellular carcinoma (E-HCC) patients will develop recurrence. Dysregulated pH, a hallmark of E-HCC, is correlated with poor prognosis. The acidic microenvironment has been shown to promote...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.30958

    authors: Tian XP,Wang CY,Jin XH,Li M,Wang FW,Huang WJ,Yun JP,Xu RH,Cai QQ,Xie D

    更新日期:2019-03-16 00:00:00

  • Immunohistochemical PSMA expression patterns of primary prostate cancer tissue are associated with the detection rate of biochemical recurrence with 68Ga-PSMA-11-PET.

    abstract::Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa). Nevertheless, even at high prostate-specific antigen (PSA) levels (> 3 ng/ml), a relevant number of PSMA-PET scans are negative, mainly due to PSMA-negative PCa. Our objective was...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44584

    authors: Ferraro DA,Rüschoff JH,Muehlematter UJ,Kranzbühler B,Müller J,Messerli M,Husmann L,Hermanns T,Eberli D,Rupp NJ,Burger IA

    更新日期:2020-05-15 00:00:00

  • Type H blood vessels in bone modeling and remodeling.

    abstract::In the mammalian skeletal system, osteogenesis and angiogenesis are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling. Recent studies have expanded our knowledge about the molecular and cellular mechanisms responsible for coupling angiogenesis and bon...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.34126

    authors: Peng Y,Wu S,Li Y,Crane JL

    更新日期:2020-01-01 00:00:00

  • Forkhead box K2 promotes human colorectal cancer metastasis by upregulating ZEB1 and EGFR.

    abstract::Background: Metastasis is the major reason for high recurrence rates and poor survival among patients with colorectal cancer (CRC). However, the underlying molecular mechanism of CRC metastasis is unclear. This study aimed to investigate the role of forkhead box K2 (FOXK2), one of the most markedly increased FOX genes...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.31716

    authors: Du F,Qiao C,Li X,Chen Z,Liu H,Wu S,Hu S,Qiu Z,Qian M,Tian D,Wu K,Fan D,Nie Y,Xia L

    更新日期:2019-05-31 00:00:00

  • Molecular signatures of BRCAness analysis identifies PARP inhibitor Niraparib as a novel targeted therapeutic strategy for soft tissue Sarcomas.

    abstract::Background: Patients with advanced soft tissue sarcomas (STS) have a dismal prognosis with few effective therapeutic options. A defect in the homologous recombination repair (HRR) pathway can accumulate DNA repair errors and gene mutations, which can lead to tumorigenesis. BRCAness describes tumors with an HRR deficie...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.45763

    authors: Li H,Tu J,Zhao Z,Chen L,Qu Y,Li H,Yao H,Wang X,Lee DF,Shen J,Wen L,Huang G,Xie X

    更新日期:2020-07-25 00:00:00

  • Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer.

    abstract::Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in th...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.18563

    authors: Belz JE,Kumar R,Baldwin P,Ojo NC,Leal AS,Royce DB,Zhang D,van de Ven AL,Liby KT,Sridhar S

    更新日期:2017-09-26 00:00:00

  • Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice.

    abstract::Recently, researchers identified a distinct vessel subtype called type H vessels that couple angiogenesis and osteogenesis. We previously found that type H vessels are reduced in ovariectomy (OVX)-induced osteoporotic mice, and preosteoclasts are able to secrete platelet-derived growth factor-BB (PDGF-BB) to stimulate...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.22144

    authors: Huang J,Yin H,Rao SS,Xie PL,Cao X,Rao T,Liu SY,Wang ZX,Cao J,Hu Y,Zhang Y,Luo J,Tan YJ,Liu ZZ,Wu B,Hu XK,Chen TH,Chen CY,Xie H

    更新日期:2018-03-28 00:00:00

  • Sex Differences Revealed in a Mouse CFA Inflammation Model with Macrophage Targeted Nanotheranostics.

    abstract::Monocyte derived macrophages (MDMs) infiltrate sites of infection or injury and upregulate cyclooxygenase-2 (COX-2), an enzyme that stimulates prostaglandin-E2 (PgE2). Nanotheranostics combine therapeutic and diagnostic agents into a single nanosystem. In previous studies, we demonstrated that a nanotheranostic strate...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.41309

    authors: Liu L,Karagoz H,Herneisey M,Zor F,Komatsu T,Loftus S,Janjic BM,Gorantla VS,Janjic JM

    更新日期:2020-01-01 00:00:00

  • Sulforaphane Inhibits the Acquisition of Tobacco Smoke-Induced Lung Cancer Stem Cell-Like Properties via the IL-6/ΔNp63α/Notch Axis.

    abstract::Background: Tobacco smoke (TS) critically contributes to the development of lung cancer; however, the underlying molecular mechanisms remain unclear. The induction of cancer stem cells (CSCs) by TS represents an early event in tumor initiation. The lung cancer-related gene ΔNp63α is highly expressed in epithelial tiss...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.33812

    authors: Xie C,Zhu J,Jiang Y,Chen J,Wang X,Geng S,Wu J,Zhong C,Li X,Meng Z

    更新日期:2019-07-09 00:00:00

  • Retraction of "Tunable Plasmonic Nanoprobes for Theranostics of Prostate Cancer".

    abstract::[This retracts the article on p. 3 in vol. 1, PMID: 21547151.]. ...

    journal_title:Theranostics

    pub_type: 杂志文章,撤回出版物

    doi:10.7150/thno.18746

    authors: Lukianova-Hleb EY,Oginsky AO,Samaniego AP,Shenefelt DL,Wagner DS,Hafner JH,Farach-Carson MC,Lapotko DO

    更新日期:2017-01-07 00:00:00

  • Early Ultrafast Ultrasound Imaging of Cerebral Perfusion correlates with Ischemic Stroke outcomes and responses to treatment in Mice.

    abstract::In the field of ischemic cerebral injury, precise characterization of neurovascular hemodynamic is required to select candidates for reperfusion treatments. It is thus admitted that advanced imaging-based approaches would be able to better diagnose and prognose those patients and would contribute to better clinical ca...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44233

    authors: Hingot V,Brodin C,Lebrun F,Heiles B,Chagnot A,Yetim M,Gauberti M,Orset C,Tanter M,Couture O,Deffieux T,Vivien D

    更新日期:2020-06-12 00:00:00

  • Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA.

    abstract::Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, unders...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.27313

    authors: De Sarno F,Ponsiglione AM,Russo M,Grimaldi AM,Forte E,Netti PA,Torino E

    更新日期:2019-02-28 00:00:00

  • The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction.

    abstract::Acute myocardial infarction (AMI) is one of the leading causes of mortality around the world, and the inflammatory response plays a pivotal role in the progress of myocardial necrosis and ventricular remodeling, dysfunction and heart failure after AMI. Therapies aimed at modulating immune response after AMI on a molec...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.53326

    authors: Xiong YY,Gong ZT,Tang RJ,Yang YJ

    更新日期:2021-01-01 00:00:00

  • Real time dynamic imaging and current targeted therapies in the war on cancer: a new paradigm.

    abstract::In biology, as every science student is made to learn, ontology recapitulates phylogeny. In medicine, however, oncology recapitulates polemology, the science of warfare: The medical establishment is transitioning from highly toxic poisons that kill rapidly dividing normal and malignant cells with little specificity to...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.5658

    authors: Paulmurugan R,Oronsky B,Brouse CF,Reid T,Knox S,Scicinski J

    更新日期:2013-05-25 00:00:00

  • FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism.

    abstract::Patients with cervical cancer (CCa) with lymph node metastasis (LNM) have an extremely poor prognosis. Elucidation of the molecular mechanisms underlying LNM may provide clinical therapeutic strategies for CCa. Upregulation of fatty acid-binding protein 5 (FABP5) expression in CCa tumours was demonstrated to positivel...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44868

    authors: Zhang C,Liao Y,Liu P,Du Q,Liang Y,Ooi S,Qin S,He S,Yao S,Wang W

    更新日期:2020-05-17 00:00:00