The cell-penetrating FOXM1 N-terminus (M1-138) demonstrates potent inhibitory effects on cancer cells by targeting FOXM1 and FOXM1-interacting factor SMAD3.

Abstract:

:Transcription factor FOXM1 is involved in stimulating cell proliferation, enhancing DNA damage repair, promoting metastasis of cancer cells, and the inhibition of FOXM1 has been shown to prevent the initiation and progression of multiple cancers and FOXM1 is considered to be an effective target for tumor therapeutic drug development. The N-terminus of FOXM1 has been found to prevent transcriptional activities of FOXM1 and to mediate the interaction between FOXM1 and SMAD3. METHODS:A recombinant FOXM1 N-terminal domain (1-138aa) fused with a nine arginine cell-penetrating peptide is produced with an E. coli expression system and named as M1-138. The effects of M1-138 on the proliferation, migration, and tumorigenic ability of cancer cells are analyzed in vitro with cell counting, transwell assays, and colony formation assays. Electrophoretic mobility shift assays (EMSAs) and Luciferase activity assays are used to test the DNA binding ability and transcriptional activity of transcription factors. The levels of mRNAs and proteins are measured by quantitative-PCR, Western blotting or Immunohistochemistry. The interactions among proteins are analyzed with Pull-down and Co-immunoprecipitation (Co-IP) assays. The nude mouse engrafted tumor models are used to test the inhibitory effects of M1-138 in vivo. RESULTS:M1-138 diminishes the proliferation and migration abilities of cancer cells through binding to FOXM1 and FOXM1-interacting factor SMAD3, and consequently attenuating FOXM1 transcriptional activities from both direct and indirect FOXM1-promoter binding mechanisms and interfering with the interaction between FOXM1 and SMAD3. Treatment of M1-138 prevents tumorigenicity of cancer cells and inhibits tumor growth in nude mouse xenograft models with no obvious signs of toxicity. CONCLUSION:M1-138 is a promising drug candidate for the development of anti-cancer therapeutics targeting FOXM1 and SMAD3.

journal_name

Theranostics

journal_title

Theranostics

authors

Zhang Z,Bu H,Yu J,Chen Y,Pei C,Yu L,Huang X,Tan G,Tan Y

doi

10.7150/thno.32693

subject

Has Abstract

pub_date

2019-04-25 00:00:00

pages

2882-2896

issue

10

issn

1838-7640

pii

thnov09p2882

journal_volume

9

pub_type

杂志文章
  • Aptamer-Based Therapeutic Approaches to Target Cancer Stem Cells.

    abstract::Cancer stem cells (CSCs) are believed to be a principal cellular source for tumour progression and therapeutic drug resistance as they are capable of self-renewal and can differentiate into cancer cells. Importantly, CSCs acquire the ability to evade the killing effects of cytotoxic agents through changes at the genet...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.20725

    authors: Zhou G,Latchoumanin O,Bagdesar M,Hebbard L,Duan W,Liddle C,George J,Qiao L

    更新日期:2017-09-13 00:00:00

  • Antitumoral effects of pharmacological ascorbate on gastric cancer cells: GLUT1 expression may not tell the whole story.

    abstract::The recently reported results of Lu et al. (Theranostics. 2018; 8: 1312-26) - highlighting GLUT1 expression as a marker for sensitivity of gastric cancer cells to therapeutic doses of ascorbate - are discussed in the light of additional factors potentially affecting the underlying processes, such as the concomitant ex...

    journal_title:Theranostics

    pub_type: 评论,社论

    doi:10.7150/thno.29864

    authors: Corti A,Belcastro E,Pompella A

    更新日期:2018-11-15 00:00:00

  • Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy.

    abstract::Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.46006

    authors: Hu J,Li Y,Li H,Shi F,Xie L,Zhao L,Tang M,Luo X,Jia W,Fan J,Zhou J,Gao Q,Qiu S,Wu W,Zhang X,Liao W,Bode AM,Cao Y

    更新日期:2020-10-25 00:00:00

  • Multivalent Targeting Based Delivery of Therapeutic Peptide using AP1-ELP Carrier for Effective Cancer Therapy.

    abstract::Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell-targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.16425

    authors: Sarangthem V,Kim Y,Singh TD,Seo BY,Cheon SH,Lee YJ,Lee BH,Park RW

    更新日期:2016-09-25 00:00:00

  • Membrane Radiolabelling of Exosomes for Comparative Biodistribution Analysis in Immunocompetent and Immunodeficient Mice - A Novel and Universal Approach.

    abstract::Extracellular vesicles, in particular exosomes, have recently gained interest as novel drug delivery vectors due to their biological origin and inherent intercellular biomolecule delivery capability. An in-depth knowledge of their in vivo biodistribution is therefore essential. This work aimed to develop a novel, reli...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.27891

    authors: Faruqu FN,Wang JT,Xu L,McNickle L,Chong EM,Walters A,Gurney M,Clayton A,Smyth LA,Hider R,Sosabowski J,Al-Jamal KT

    更新日期:2019-02-28 00:00:00

  • Nanofibrous nerve guidance conduits decorated with decellularized matrix hydrogel facilitate peripheral nerve injury repair.

    abstract::Rationale: Peripheral nerve injury (PNI) is a great challenge for regenerative medicine. Nerve autograft is the gold standard for clinical PNI repair. Due to its significant drawbacks, artificial nerve guidance conduits (NGCs) have drawn much attention as replacement therapies. We developed a combinatorial NGC consist...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.50825

    authors: Zheng C,Yang Z,Chen S,Zhang F,Rao Z,Zhao C,Quan D,Bai Y,Shen J

    更新日期:2021-01-01 00:00:00

  • Glyco-Dendrimers as Intradermal Anti-Tumor Vaccine Targeting Multiple Skin DC Subsets.

    abstract::The human skin is an attractive anti-tumor vaccination site due to the vast network of dendritic cell (DC) subsets that carry antigens to the draining lymph nodes and stimulate tumor specific CD4+ and CD8+ T cells in. Specific vaccine delivery to skin DC can be accomplished by targeting glycan coated antigens to C-typ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35059

    authors: Duinkerken S,Horrevorts SK,Kalay H,Ambrosini M,Rutte L,de Gruijl TD,Garcia-Vallejo JJ,van Kooyk Y

    更新日期:2019-08-12 00:00:00

  • Membrane TLR9 Positive Neutrophil Mediated MPLA Protects Against Fatal Bacterial Sepsis.

    abstract::Sepsis is a major cause of patient mortality and morbidity from bacterial infections. Although neutrophils are known to be important in the development of sepsis, how distinctive neutrophil subtypes regulate inflammatory processes involved in septicemia remains unclear. Preconditioning protects organisms against subse...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.37139

    authors: Yang Z,Wang L,Yu H,Wang R,Gou Y,Zhang M,Kang C,Liu T,Lan Y,Wang X,Liu J,Cooper MA,Li X,Yue K,Yu Y,Wang L,Kim BYS,Jiang W,Sun W

    更新日期:2019-08-14 00:00:00

  • Focused ultrasound as a novel strategy for noninvasive gene delivery to retinal Müller glia.

    abstract::Müller glia are specialized retinal cells with stem cell properties in fish and frogs but not in mammals. Current efforts to develop gene therapies to activate mammalian Müller glia for retinal repair will require safe and effective delivery strategies for recombinant adeno-associated viruses (AAVs), vectors of choice...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.42611

    authors: Touahri Y,Dixit R,Kofoed RH,Miloska K,Park E,Raeisossadati R,Markham-Coultes K,David LA,Rijal H,Zhao J,Lynch M,Hynynen K,Aubert I,Schuurmans C

    更新日期:2020-02-10 00:00:00

  • Melanocortin 1 receptor attenuates early brain injury following subarachnoid hemorrhage by controlling mitochondrial metabolism via AMPK/SIRT1/PGC-1α pathway in rats.

    abstract::Mitochondria-mediated oxidative stress and apoptosis contribute greatly to early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study hypothesized that activation of melanocortin 1 receptor (MC1R), using BMS-470539, attenuates EBI by controlling mitochondrial metabolism after SAH. Methods: We utilize...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.49426

    authors: Xu W,Yan J,Ocak U,Lenahan C,Shao A,Tang J,Zhang J,Zhang JH

    更新日期:2021-01-01 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

  • Dual inhibition of PFKFB3 and VEGF normalizes tumor vasculature, reduces lactate production, and improves chemotherapy in glioblastoma: insights from protein expression profiling and MRI.

    abstract::Rationale: Tumor vascular normalization (TVN) is emerging to enhance the efficacy of anticancer treatment in many cancers including glioblastoma (GBM). However, a common and severe challenge being currently faced is the transient TVN effect, hampering the sustained administration of anticancer therapy during TVN windo...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44427

    authors: Zhang J,Xue W,Xu K,Yi L,Guo Y,Xie T,Tong H,Zhou B,Wang S,Li Q,Liu H,Chen X,Fang J,Zhang W

    更新日期:2020-06-05 00:00:00

  • Charge and hydrophobicity effects of NIR fluorophores on bone-specific imaging.

    abstract::Recent advances in near-infrared (NIR) fluorescence imaging enabled real-time intraoperative detection of bone metastases, bone growth, and tissue microcalcification. Pamidronate (PAM) has been widely used for this purpose because of its high binding affinity toward bone and remarkable therapeutic effects. Herein we d...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.11222

    authors: Bao K,Nasr KA,Hyun H,Lee JH,Gravier J,Gibbs SL,Choi HS

    更新日期:2015-03-01 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

  • 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

  • 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

  • Lymphocytic subsets play distinct roles in heart diseases.

    abstract::Heart diseases are one of the leading causes of death for humans in the world. Increasing evidence has shown that myocardial injury induced innate and adaptive immune responses upon early cellular damage but also during chronic phases post-injury. The immune cells can not only aggravate the injury but also play an ess...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.33112

    authors: Wang J,Duan Y,Sluijter JP,Xiao J

    更新日期:2019-05-31 00:00:00

  • All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide.

    abstract::Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic. Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy....

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.41382

    authors: Ran D,Zhou J,Chai Z,Li J,Xie C,Mao J,Lu L,Zhang Y,Wu S,Zhan C,Lu W

    更新日期:2020-03-04 00:00:00

  • Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy.

    abstract::Many drug controlled release methods have been integrated in multifunctional nanoparticles, such as pH-, redox-, temperature-, enzyme-, and light-responsive release. However, few report is associated with the ROS responsive drug controlled release. Herein, a thioketal linker-based ROS responsive drug (camptothecin con...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.14101

    authors: Yue C,Zhang C,Alfranca G,Yang Y,Jiang X,Yang Y,Pan F,de la Fuente JM,Cui D

    更新日期:2016-02-05 00:00:00

  • Spontaneous evolution of human skin fibroblasts into wound-healing keratinocyte-like cells.

    abstract::Producing keratinocyte cells (KCs) in large scale is difficult due to their slow proliferation, disabling their use as seed cells for skin regeneration and wound healing. Cell reprogramming is a promising inducer-based approach to KC production but only reaches very low cellular conversion. Here we reported a unique c...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.31526

    authors: Zhang F,Zhang D,Cheng K,Zhou Z,Liu S,Chen L,Hu Y,Mao C,Liu S

    更新日期:2019-07-09 00:00:00

  • A skeleton muscle model using GelMA-based cell-aligned bioink processed with an electric-field assisted 3D/4D bioprinting.

    abstract::The most important requirements of biomedical substitutes used in muscle tissue regeneration are appropriate topographical cues and bioactive components for the induction of myogenic differentiation/maturation. Here, we developed an electric field-assisted 3D cell-printing process to fabricate cell-laden fibers with a...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.50794

    authors: Yang GH,Kim W,Kim J,Kim G

    更新日期:2021-01-01 00:00:00

  • Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells.

    abstract::Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs w...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.15359

    authors: Chen JF,Zhu Y,Lu YT,Hodara E,Hou S,Agopian VG,Tomlinson JS,Posadas EM,Tseng HR

    更新日期:2016-06-15 00:00:00

  • CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways.

    abstract::Metastasis is a major cause of death in patients with colorectal cancer (CRC). Cysteine-rich protein 2 (CSRP2) has been recently implicated in the progression and metastasis of a variety of cancers. However, the biological functions and underlying mechanisms of CSRP2 in the regulation of CRC progression are largely un...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.45674

    authors: Chen L,Long X,Duan S,Liu X,Chen J,Lan J,Liu X,Huang W,Geng J,Zhou J

    更新日期:2020-09-02 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

  • Detection of high-risk atherosclerotic plaques with ultrasound molecular imaging of glycoprotein IIb/IIIa receptor on activated platelets.

    abstract:OBJECTIVE:Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated plat...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.10020

    authors: Guo S,Shen S,Wang J,Wang H,Li M,Liu Y,Hou F,Liao Y,Bin J

    更新日期:2015-02-05 00:00:00

  • Dual-Channel Fluorescence Imaging of Hydrogel Degradation and Tissue Regeneration in the Brain.

    abstract::The ability of brain tissue to regenerate is limited; therefore, brain diseases (i.e., trauma, stroke, tumors) often lead to irreversible motor and cognitive impairments. Therapeutic interventions using various types of injectable biomaterials have been investigated to promote endogenous neural differentiation. Despit...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35606

    authors: Park GK,Kim SH,Kim K,Das P,Kim BG,Kashiwagi S,Choi HS,Hwang NS

    更新日期:2019-05-31 00:00:00

  • Roles of long non-coding RNAs and emerging RNA-binding proteins in innate antiviral responses.

    abstract::The diseases caused by viruses posed a great challenge to human health, the development of which was driven by the imbalanced host immune response. Host innate immunity is an evolutionary old defense system that is critical for the elimination of the virus. The overactive innate immune response also leads to inflammat...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.48520

    authors: Wang Y,Wang Y,Luo W,Song X,Huang L,Xiao J,Jin F,Ren Z,Wang Y

    更新日期:2020-07-23 00:00:00

  • Intravital molecular imaging reveals the restrained capacity of CTLs in the killing of tumor cells in the liver.

    abstract::Cytotoxic T lymphocytes (CTLs) and their gene-engineered cells display great application prospects in tumor immunotherapy. The timing of CTL-induced molecular events in tumor cells is unclear, and we also unknow whether the killing efficiency of CTLs is restrained in the liver, an immunotolerant organ with a high tumo...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44979

    authors: Liu L,Dai B,Li R,Liu Z,Zhang Z

    更新日期:2021-01-01 00:00:00

  • Nondestructive Analysis of Tumor-Associated Membrane Protein Integrating Imaging and Amplified Detection in situ Based on Dual-Labeled DNAzyme.

    abstract::Comprehensive analysis of the expression level and location of tumor-associated membrane proteins (TMPs) is of vital importance for the profiling of tumor cells. Currently, two kinds of independent techniques, i.e. ex situ detection and in situ imaging, are usually required for the quantification and localization of T...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.22794

    authors: Chen X,Zhao J,Chen T,Gao T,Zhu X,Li G

    更新日期:2018-01-01 00:00:00

  • Labeling human mesenchymal stem cells with gold nanocages for in vitro and in vivo tracking by two-photon microscopy and photoacoustic microscopy.

    abstract::Stem cell tracking is a highly important subject. Current techniques based on nanoparticle-labeling, such as magnetic resonance imaging, fluorescence microscopy, and micro-computed tomography, are plagued by limitations including relatively low sensitivity or penetration depth, involvement of ionizing irradiation, and...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.5369

    authors: Zhang YS,Wang Y,Wang L,Wang Y,Cai X,Zhang C,Wang LV,Xia Y

    更新日期:2013-07-19 00:00:00