Open Access

ARTICLE

DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity

Oncology Research, DOI:10.32604/or.2023.030304
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
Abstract C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein C-mannosylation are not yet fully understood, especially in tumor progression. Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells, enabling the tumors to form matrix-embedded vasculogenic structures, containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors. In this study, we focused on DPY19L3, a C-mannosyltransferase, and aimed to unravel its role in… More >

View

186

Download

49

Open Access

ARTICLE

DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity

Oncology Research, Vol.32, No.4, pp. 607-614, 2024, DOI:10.32604/or.2023.030304
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
Abstract

C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein C-mannosylation are not yet fully understood, especially in tumor progression. Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells, enabling the tumors to form matrix-embedded vasculogenic structures, containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors. In this study, we focused on DPY19L3, a C-mannosyltransferase, and aimed to unravel its role in… More >

View

1796

Download

393

Open Access

ARTICLE

Cisplatin-induced activation of TGF-β signaling contributes to drug resistance

Oncology Research, Vol.32, No.1, pp. 139-150, 2024, DOI:10.32604/or.2023.030190
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
Abstract Growing evidence suggests an association between epithelial-mesenchymal transition (EMT), a hallmark of tumor malignancy, and chemoresistance to a number of anti-cancer drugs. However, the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear. To address this issue, we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts. In these clones, the epithelial marker E-cadherin was downregulated, whereas the mesenchymal marker N-cadherin was upregulated. Moreover, the expression of EMT-related transcription factors, including Slug, was elevated. On the other hand, the upregulation of other mesenchymal marker Vimentin… More >

View

456

Download

335

Open Access

ARTICLE

Identification of a dihydroorotate dehydrogenase inhibitor that inhibits cancer cell growth by proteomic profiling

Oncology Research, Vol.31, No.6, pp. 833-844, 2023, DOI:10.32604/or.2023.030241
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
Abstract Dihydroorotate dehydrogenase (DHODH) is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases. This study presents the identification of a potent DHODH inhibitor by proteomic profiling. Cell-based screening revealed that NPD723, which is reduced to H-006 in cells, strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells. H-006 also suppressed the growth of various cancer cells. Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors. H-006 potently inhibited human DHODH activity in vitro, whereas NPD723 was approximately… More >

View

964

Download

442

Like

1

Open Access

ARTICLE

Deoxynortryptoquivaline: A unique antiprostate cancer agent

Oncology Research, Vol.31, No.6, pp. 845-853, 2023, DOI:10.32604/or.2023.030266
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
Abstract The androgen receptor (AR) is a critical target in all the clinical stages of prostate cancer. To identify a new AR inhibitor, we constructed a new screening system using the androgen-dependent growth of prostate cancer cell lines as a screening indicator. We screened 50,000 culture broths of microorganisms using this screening system and found that the fermentation broth produced by a fungus inhibited androgen-dependent growth of human prostate cancer LNCaP cells without cytotoxicity. Purification of this culture medium was performed, and this resulted in deoxynortryptoquivaline (DNT) being identified as a novel inhibitor of AR function. DNT showed potent inhibition of… More >

Graphic Abstract

View

1222

Download

239

Open Access

ARTICLE

Isolation and characterization of β-transducin repeat-containing protein ligands screened using a high-throughput screening system

Oncology Research, Vol.31, No.5, pp. 645-654, 2023, DOI:10.32604/or.2023.030240
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
Abstract β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCF^β-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the TNFα-induced degradation of… More >

Graphic Abstract

View

1826

Download

364

Open Access

ARTICLE

Identification of microbial metabolites that accelerate the ubiquitin-dependent degradation of c-Myc

Oncology Research, Vol.31, No.5, pp. 655-666, 2023, DOI:10.32604/or.2023.030248
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
Abstract

Myc belongs to a family of proto-oncogenes that encode transcription factors. The overexpression of c-Myc causes many types of cancers. Recently, we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical library. The specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be explained. In this study, we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces sp. RK19-A0402 strongly inhibits c-Myc transcriptional activity. After purification of the hit broth, we identified compounds closely related to the aglycone of cytovaricin and had… More >

Graphic Abstract

View

2005

Download

564