Up-regulation of EMT-related gene VCAN by NPM1 mutant-driven TGF- β /cPML signalling promotes leukemia cell invasion

In this study, we identified the EMT-related gene versican (VCAN) in NPM1-mutated AML across three patient datasets. Further experiments validated the elevated VCAN expression in NPM1-mutated AML primary blasts and OCI-AML3 cells with NPM1 mutation. Mechanistic studies revealed that increased VCAN expression was at least partially regulated by NPM1 mutant via TGF-β/cPML/Smad signalling. Functional evaluations showed that silencing VCAN by shRNA significantly suppressed cell migration and invasion capacity, whereas increased VCAN by overexpressing NPM1-mA enhanced migration and invasion ability of leukemia cells. Finally, we found that high expression of VCAN was associated with poor prognosis in AML patients. These findings provide insights into the involvement of EMT-related gene VCAN in the pathogenesis of NPM1-mutated leukemia, which suggests that VCAN is an attractive target for novel diagnostic and therapeutic strategies in NPM1-mutated AML.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research

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Abstract Epithelial growth factor-like 7 (EGFL7) is a secretory protein with a well-characterized role in angiogenesis and the oncogenesis of certain solid tumors. Overexpression of EGFL7 is associated with adverse prognosis in patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, whether this association persists after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To further clarify the prognostic role of EGFL7, seventy-one AML patients with EGFL7 expression data who underwent allo-HSCT from The Cancer Genome Atlas database were included and divided into ...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
CONCLUSIONS: Our data not only define the essential role of TWIST1 as an EMT-TF in APL patients but also suggest that disrupting the TRIB3/TWIST1 interaction reverses induction therapy resistance and blocks rapid progression of APL early death. PMID: 31235507 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study we tested the clinoptilolite, chabazite, and natrolite ability to be loaded by antitumor ribonuclease binase and the cytotoxicity of the obtained complexes. We found the optimal conditions for binase loading into zeolites and established the dynamic of its release. Cytotoxic effects of zeolite-binase complexes toward colorectal cancer Caco2 cells were characterized after 24 and 48 h of incubation with cells using MTT-test. Zeolites were toxic by itselfs and reduced cells viability by 30% (clinoptilolite), 40% (chabazite), and 70% (natrolite) after 48 h of incubation. Binase complexes with clinoptilolite as we...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Li Liu, Jiajing Lin and Hongying He* Department of Obstetrics and Gynecology, Liuzhou Worker’s Hospital, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China Background and Objective: Endometrial cancer (EC) is a common gynecological malignancy worldwide. Despite advances in the development of strategies for treating EC, prognosis of the disease remains unsatisfactory, especially for advanced EC. The aim of this study was to identify novel genes that can be used as potential biomarkers for identifying the prognosis of EC and to construct a novel risk stratification using these genes. Me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients. Introduction DNA methyltransferase inhibitors (DNMTi) are widely used as chemical tools for hypomethylating the genome, with an aim to understand the role of DNA methylation in multiple processes (e.g., X-chromosome inactivation and DNA imprinting) and as an anti-ca...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion and Perspective With in-depth understandings of antibodies, linkers, and payloads, ADCs have also achieved great development. The linkage strategy and target diversity have already improved the delivery of the payloads to tumor tissues and reduced exposure to normal tissues. With the development of payloads, some novel potent payloads are used by ADCs, which allows researchers to exploit novel linkers to attach the antibody and payloads without disturbing their potency (Dragovich et al., 2018). Furthermore, some irrelevant antigen-target ADCs also may exert toxicity to tumor cells due to the vascular gap of tum...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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