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 in CRC, and the mechanism by which it is deregulated in CRC metastasis. Methods: FOXK2 levels were analyzed in two independent human CRC cohorts (cohort I, n = 363; cohort II, n = 390). In vitro Transwell assays and in vivo lung and liver metastasis models were used to examine CRC cell migration, invasion and metastasis. Chromatin immunoprecipitation and luciferase reporter assays were used to measure the binding of transcription factors to the promoters of FOXK2, zinc finger E-box binding homeobox 1 (ZEB1) and epidermal growth factor receptor (EGFR). Cetuximab was utilized to treat FOXK2-mediated metastatic CRC. Results: FOXK2 was significantly upregulated in human CRC tissues, was correlated with more aggressive features and indicated a poor prognosis. FOXK2 overexpression promoted CRC migration, invasion and metastasis, while FOXK2 downregulation had the opposite effects. ZEB1 and EGFR were determined to be direct transcriptional targets of FOXK2 and were essential for FOXK2-mediated CRC metastasis. Moreover, activation of EGFR signaling by EGF enhanced FOXK2 expression via the extracellular regulated protein kinase (ERK) and nuclear factor (NF)-κB pathways. The EGFR monoclonal antibody cetuximab significantly inhibited FOXK2-promoted CRC metastasis. In clinical CRC tissues, FOXK2 expression was positively correlated with the expression of p65, ZEB1 and EGFR. CRC patients who coexpressed p65/FOXK2, FOXK2/ZEB1 and FOXK2/EGFR had poorer prognosis. Conclusions: FOXK2 serves as a prognostic biomarker in CRC. Cetuximab can block the EGF-NF-κB-FOXK2-EGFR feedback loop and suppress CRC metastasis.

journal_name

Theranostics

journal_title

Theranostics

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

doi

10.7150/thno.31716

subject

Has Abstract

pub_date

2019-05-31 00:00:00

pages

3879-3902

issue

13

issn

1838-7640

pii

thnov09p3879

journal_volume

9

pub_type

杂志文章
  • Multiplexed non-invasive tumor imaging of glucose metabolism and receptor-ligand engagement using dark quencher FRET acceptor.

    abstract::Rationale: Following an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imag...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.45825

    authors: Rudkouskaya A,Sinsuebphon N,Ochoa M,Chen SJ,Mazurkiewicz JE,Intes X,Barroso M

    更新日期:2020-08-15 00:00:00

  • Integrin targeted delivery of radiotherapeutics.

    abstract::Targeted radionuclide therapy, which is based on the selective delivery of a sufficient radiation dose to tumors without significantly affecting normal tissues, is a promising therapeutic approach for the treatment of a wide variety of malignancies. Integrins, a family of cell adhesion molecules, play key roles during...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno/v01p0201

    authors: Liu Z,Wang F,Chen X

    更新日期:2011-03-01 00:00:00

  • Drug Repurposing Screening Identifies Tioconazole as an ATG4 Inhibitor that Suppresses Autophagy and Sensitizes Cancer Cells to Chemotherapy.

    abstract::Background: Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy. However, this theory in clinical cancer research remains controversial due to the limited number of drugs that speci...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.22012

    authors: Liu PF,Tsai KL,Hsu CJ,Tsai WL,Cheng JS,Chang HW,Shiau CW,Goan YG,Tseng HH,Wu CH,Reed JC,Yang LW,Shu CW

    更新日期:2018-01-01 00:00:00

  • Applications of magnetic microbubbles for theranostics.

    abstract::Compared with other diagnostic methods, ultrasound is proven to be a safe, simple, non-invasive and cost-effective imaging technique, but the resolution is not comparable to that of magnetic resonance imaging (MRI). Contrast-enhanced ultrasound employing microbubbles can gain a better resolution and is now widely used...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.3464

    authors: Cai X,Yang F,Gu N

    更新日期:2012-01-01 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

  • Mitochondrial PAK6 inhibits prostate cancer cell apoptosis via the PAK6-SIRT4-ANT2 complex.

    abstract::Rationale: P21-activated kinase 6 (PAK6) is a member of the class II PAKs family, which is a conserved family of serine/threonine kinases. Although the effects of PAK6 on many malignancies, especially in prostate cancer, have been studied for a long time, the role of PAK6 in mitochondria remains unknown. Methods: The ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.42874

    authors: Li T,Li Y,Liu T,Hu B,Li J,Liu C,Liu T,Li F

    更新日期:2020-02-03 00:00:00

  • Theranostic nanobubble encapsulating a plasmon-enhanced upconversion hybrid nanosystem for cancer therapy.

    abstract::Nanobubble (NB), which simultaneously enhances ultrasound (US) images and access therapeutic platforms, is required for future cancer treatment. Methods: We designed a theranostic agent for novel cancer treatment by using an NB-encapsulated hybrid nanosystem that can be monitored by US and fluorescent imaging and acti...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.38684

    authors: Huang WT,Chan MH,Chen X,Hsiao M,Liu RS

    更新日期:2020-01-01 00:00:00

  • Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function.

    abstract::The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.21234

    authors: Hu Y,Rao SS,Wang ZX,Cao J,Tan YJ,Luo J,Li HM,Zhang WS,Chen CY,Xie H

    更新日期:2018-01-01 00:00:00

  • Blocking the 4-1BB Pathway Ameliorates Crystalline Silica-induced Lung Inflammation and Fibrosis in Mice.

    abstract::Long term pulmonary exposure to crystalline silica leads to silicosis that manifests progressive interstitial fibrosis, eventually leading to respiratory failure and death. Despite efforts to eliminate silicosis, clinical cases continue to occur in both developing and developed countries. The exact mechanisms of cryst...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.16180

    authors: Li C,Du S,Lu Y,Lu X,Liu F,Chen Y,Weng D,Chen J

    更新日期:2016-09-09 00:00:00

  • Imaging and therapy of ovarian cancer: clinical application of nanoparticles and future perspectives.

    abstract::Despite significant advances in cancer diagnostics and treatment, ovarian cancers (OC) continue to kill more than 150,000 women every year worldwide. Due to the relatively asymptomatic nature and the advanced stage of the disease at the time of diagnosis, OC is the most lethal gynecologic malignancy. The current treat...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.26345

    authors: Di Lorenzo G,Ricci G,Severini GM,Romano F,Biffi S

    更新日期:2018-07-30 00:00:00

  • Activation of EP4 receptor limits transition of acute to chronic heart failure in lipoxygenase deficient mice.

    abstract::Aim: Immune responsive 12/15 lipoxygenase (12/15LOX)-orchestrate biosynthesis of essential inflammation-resolution mediators during acute inflammatory response in post-myocardial infarction (MI). Lack of 12/15LOX dampens proinflammatory mediator 12-(S)-hydroxyeicosatetraenoic acid (12-(S)-HETE), improves post-MI survi...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.51183

    authors: Kain V,Ingle KA,Rajasekaran NS,Halade GV

    更新日期:2021-01-01 00:00:00

  • Determination of cerebrospinal fluid leakage by selective deletion of transferrin glycoform using an immunochromatographic assay.

    abstract::Cerebrospinal fluid (CSF) leakage can lead to brain and spine pathologies and there is an urgent need for a rapid diagnostic method for determining CSF leakage. Beta-2 transferrin (β2TF), asialotransferrin, is a specific CSF glycoprotein biomarker used to determine CSF leakage when distinguished from serum sialotransf...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.34411

    authors: Oh J,Kwon SJ,Dordick JS,Sonstein WJ,Linhardt RJ,Kim MG

    更新日期:2019-05-31 00:00:00

  • Nuclear translocation of PLSCR1 activates STAT1 signaling in basal-like breast cancer.

    abstract::Rationale: Basal-like breast cancer (BLBC) is associated with high grade, distant metastasis, and poor prognosis; however, the mechanism underlying aggressiveness of BLBC is still unclear. Emerging evidence has suggested that phospholipid scramblase 1 (PLSCR1) is involved in tumor progression. Here, we aimed to study ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.43150

    authors: Huang P,Liao R,Chen X,Wu X,Li X,Wang Y,Cao Q,Dong C

    更新日期:2020-03-25 00:00:00

  • Ultrasmall gold nanoparticles in cancer diagnosis and therapy.

    abstract::Due to their lower systemic toxicity, faster kidney clearance and higher tumor accumulation, ultrasmall gold nanoparticles (less than 10 nm in diameter) have been proved to be promising in biomedical applications. However, their potential applications in cancer imaging and treatment have not been reviewed yet. This re...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.42471

    authors: Fan M,Han Y,Gao S,Yan H,Cao L,Li Z,Liang XJ,Zhang J

    更新日期:2020-03-31 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

  • Establishing sheep as an experimental species to validate ultrasound-mediated blood-brain barrier opening for potential therapeutic interventions.

    abstract::Rationale: Treating diseases of the brain such as Alzheimer's disease (AD) is challenging as the blood-brain barrier (BBB) effectively restricts access of a large number of potentially useful drugs. A potential solution to this problem is presented by therapeutic ultrasound, a novel treatment modality that can achieve...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.22852

    authors: Pelekanos M,Leinenga G,Odabaee M,Odabaee M,Saifzadeh S,Steck R,Götz J

    更新日期:2018-04-03 00:00:00

  • Sonodynamic therapy-induced foam cells apoptosis activates the phagocytic PPARγ-LXRα-ABCA1/ABCG1 pathway and promotes cholesterol efflux in advanced plaque.

    abstract::In advanced atherosclerotic plaques, defective efferocytosis of apoptotic foam cells and decreased cholesterol efflux contribute to lesion progression. In our previous study, we demonstrated that 5-aminolevulinic acid (ALA)-mediated sonodynamic therapy (SDT) could induce foam cells apoptosis via the mitochondrial-casp...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.26193

    authors: Wang H,Yang Y,Sun X,Tian F,Guo S,Wang W,Tian Z,Jin H,Zhang Z,Tian Y

    更新日期:2018-09-29 00:00:00

  • Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing.

    abstract::RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.7866

    authors: Gao S,Hein S,Dagnæs-Hansen F,Weyer K,Yang C,Nielsen R,Christensen EI,Fenton RA,Kjems J

    更新日期:2014-08-13 00:00:00

  • Lentivirus-mediated IL-10-expressing Bone Marrow Mesenchymal Stem Cells promote corneal allograft survival via upregulating lncRNA 003946 in a rat model of corneal allograft rejection.

    abstract::Rationale: Corneal transplantation is an effective treatment to corneal blindness. However, the immune rejection imperils corneal allograft survival. An interventional modality is urgently needed to inhibit immune rejection and promote allograft survival. In our previous study, subconjunctival injections of bone marro...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.31711

    authors: Lu X,Ru Y,Chu C,Lv Y,Gao Y,Jia Z,Huang Y,Zhang Y,Zhao S

    更新日期:2020-07-09 00:00:00

  • Glioma Dual-Targeting Nanohybrid Protein Toxin Constructed by Intein-Mediated Site-Specific Ligation for Multistage Booster Delivery.

    abstract::Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the im...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.20578

    authors: Chen Y,Zhang M,Jin H,Li D,Xu F,Wu A,Wang J,Huang Y

    更新日期:2017-08-15 00:00:00

  • Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study.

    abstract::Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and sa...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.23335

    authors: Hekman MC,Rijpkema M,Muselaers CH,Oosterwijk E,Hulsbergen-Van de Kaa CA,Boerman OC,Oyen WJ,Langenhuijsen JF,Mulders PF

    更新日期:2018-03-08 00:00:00

  • Drug-delivering-drug platform-mediated potent protein therapeutics via a non-endo-lysosomal route.

    abstract::Protein therapeutics is playing an increasingly critical role in treatment of human diseases. However, current vectors are captured by the digestive endo-lysosomal system, which results in an extremely low fraction (<2%) of protein being released in the cytoplasm. This paper reports a drug-delivering-drug platform (HA...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.23804

    authors: Xin X,Teng C,Du X,Lv Y,Xiao Q,Wu Y,He W,Yin L

    更新日期:2018-06-06 00:00:00

  • Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma.

    abstract::Salivary adenoid cystic carcinoma (SACC) is a peculiar malignant tumor, characterized by its slow but inexorable growth, with a high incidence of lung metastasis and poor prognosis. Here, we show the upregulated expression of EGFR ligand epiregulin in a subset of SACC cells correlates with lung metastasis and unfavora...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.19712

    authors: Yang WW,Yang LQ,Zhao F,Chen CW,Xu LH,Fu J,Li SL,Ge XY

    更新日期:2017-08-23 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

  • [18F]Tetrafluoroborate ([18F]TFB) and its analogs for PET imaging of the sodium/iodide symporter.

    abstract::Sodium/iodide symporter (NIS)-mediated iodide uptake in thyroid follicular cells is the basis of clinical utilization of radioiodines. The cloning of the NIS gene enabled applications of NIS as a reporter gene in both preclinical and translational research. Non-invasive NIS imaging with radioactive iodides and iodide ...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.24997

    authors: Jiang H,DeGrado TR

    更新日期:2018-06-24 00:00:00

  • Designing 3D Mesenchymal Stem Cell Sheets Merging Magnetic and Fluorescent Features: When Cell Sheet Technology Meets Image-Guided Cell Therapy.

    abstract::Cell sheet technology opens new perspectives in tissue regeneration therapy by providing readily implantable, scaffold-free 3D tissue constructs. Many studies have focused on the therapeutic effects of cell sheet implantation while relatively little attention has concerned the fate of the implanted cells in vivo. The ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.14064

    authors: Rahmi G,Pidial L,Silva AK,Blondiaux E,Meresse B,Gazeau F,Autret G,Balvay D,Cuenod CA,Perretta S,Tavitian B,Wilhelm C,Cellier C,Clément O

    更新日期:2016-03-21 00:00:00

  • ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon Irradiation with a Single Light Source.

    abstract::Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.15433

    authors: Yue C,Yang Y,Zhang C,Alfranca G,Cheng S,Ma L,Liu Y,Zhi X,Ni J,Jiang W,Song J,de la Fuente JM,Cui D

    更新日期:2016-10-01 00:00:00

  • A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer.

    abstract::The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.29247

    authors: Berger AW,Schwerdel D,Reinacher-Schick A,Uhl W,Algül H,Friess H,Janssen KP,König A,Ghadimi M,Gallmeier E,Bartsch DK,Geissler M,Staib L,Tannapfel A,Kleger A,Beutel A,Schulte LA,Kornmann M,Ettrich TJ,Seufferlein T

    更新日期:2019-02-12 00:00:00

  • Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels.

    abstract::Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin, however, is typically limited to lipophilic molecules with molecular weight of < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications protein delivery may be possible in barr...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.21668

    authors: Giulbudagian M,Yealland G,Hönzke S,Edlich A,Geisendörfer B,Kleuser B,Hedtrich S,Calderón M

    更新日期:2018-01-01 00:00:00

  • Effective control of tumor growth through spatial and temporal control of theranostic sodium iodide symporter (NIS) gene expression using a heat-inducible gene promoter in engineered mesenchymal stem cells.

    abstract::Purpose: The tumor homing characteristics of mesenchymal stem cells (MSCs) make them attractive vehicles for the tumor-specific delivery of therapeutic agents, such as the sodium iodide symporter (NIS). NIS is a theranostic protein that allows non-invasive monitoring of the in vivo biodistribution of functional NIS ex...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.41489

    authors: Tutter M,Schug C,Schmohl KA,Urnauer S,Schwenk N,Petrini M,Lokerse WJM,Zach C,Ziegler S,Bartenstein P,Weber WA,Wagner E,Lindner LH,Nelson PJ,Spitzweg C

    更新日期:2020-03-15 00:00:00