Mucin5AC promotes breast cancer brain metastasis through cMET/CD44v6.

Purpose: Breast cancer (BC) brain metastasis (BrM) remains a significant clinical problem. Mucins have been implicated in metastasis; however, if they are also involved in BCBrM remains unknown. We queried BrM patient databases and found Mucin 5AC (MUC5AC) to be upregulated and therefore sought to define the role of MUC5AC in BCBrM.

Nuclear factor I/B: Duality in action in cancer pathophysiology.

The nuclear factor I (NFI) family of transcription factors plays a decisive role in organ development and maturation. Their deregulation has been linked with various diseases, most notably cancer. NFIB stands apart from the other NFI family members given its unique ability to drive both tumor suppressive and oncogenic programs.

Muc4 loss mitigates epidermal growth factor receptor activity essential for PDAC tumorigenesis.

Mucin4 (MUC4) appears early during pancreatic intraepithelial neoplasia-1 (PanIN1), coinciding with the expression of epidermal growth factor receptor-1 (EGFR). The EGFR signaling is required for the onset of Kras-driven pancreatic ductal adenocarcinoma (PDAC); however, the players and mechanisms involved in sustained EGFR signaling in early PanIN lesions remain elusive. We generated a unique Esai-CRISPR-based Muc4 conditional knockout murine model to evaluate its effect on PDAC pathology.

MicroRNA-1 attenuates the growth and metastasis of small cell lung cancer through CXCR4/FOXM1/RRM2 axis.

Background: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood.

Carbon-Coated ZnS-FeS Heterostructure as an Anode Material for Lithium-Ion Battery Applications.

The construction of carbon-coated heterostructures of bimetallic sulfide is an effective technique to improve the electrochemical activity of anode materials in lithium-ion batteries. In this work, the carbon-coated heterostructured ZnS-FeS is prepared by a two-step hydrothermal method. The crystallinity and nature of carbon-coating are confirmed by the investigation of XRD and Raman spectroscopy techniques.

A Flower-like InO Catalyst Derived via Metal-Organic Frameworks for Photocatalytic Applications.

The most pressing concerns in environmental remediation are the design and development of catalysts with benign, low-cost, and efficient photocatalytic activity. The present study effectively generated a flower-like indium oxide (InO-MF) catalyst employing a convenient MOF-based solvothermal self-assembly technique. The InO-MF photocatalyst exhibits a flower-like structure, according to morphology and structural analysis.

Rethinking the chemokine cascade in brain metastasis: Preventive and therapeutic implications.

Brain metastasis (BrM) is one of the major causes of death in cancer patients and is associated with an estimated 10-40 % of total cancer cases. The survival rate of brain metastatic patients has not improved due to intratumor heterogeneity, the survival adaptations of brain homing metastatic cells, and the lack of understanding of underlying molecular mechanisms that limit the availability of effective therapies. The heterogeneous population of immune cells and tumor-initiating cells or cancer stem cells in the tumor microenvironment (TME) release various factors, such as chemokines that upon binding to their cognate receptors enhance tumor growth at primary sites and help tumor cells metastasize to the brain.

MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB).

Haploinsufficiency of chromosome 17p and c-Myc amplification distinguish group 3 medulloblastomas which are associated with early metastasis, rapid recurrence, and swift mortality. Tumor suppressor genes on this locus have not been adequately characterized. We elucidated the role of miR-212-3p in the pathophysiology of group 3 tumors.

Differential gene expression-based connectivity mapping identified novel drug candidate and improved Temozolomide efficacy for Glioblastoma.

Background: Glioblastoma (GBM) has a devastating median survival of only one year. Treatment includes resection, radiation therapy, and temozolomide (TMZ); however, the latter increased median survival by only 2.5 months in the pivotal study.

ST6GalNAc-I promotes lung cancer metastasis by altering MUC5AC sialylation.

Lung cancer (LC) is the leading cause of cancer-related mortality. However, the molecular mechanisms associated with the development of metastasis are poorly understood. Understanding the biology of LC metastasis is critical to unveil the molecular mechanisms for designing targeted therapies.

Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer.

Brain metastasis (BrM) remains a significant cause of cancer-related mortality in epidermal growth factor receptor 2-positive (ERBB2) breast cancer (BC) patients. We proposed here that a combination treatment of irreversible tyrosine kinase inhibitor neratinib (NER) and the c-MET inhibitor cabozantinib (CBZ) could prevent brain metastasis. To address this, we first tested the combination treatment of NER and CBZ in the brain-seeking ERBB2 cell lines SKBrM3 and JIMT-1-BR3, and in ERBB2 organoids that expressed the c-MET/ERBB1 axis.

RNA Polymerase II-Associated Factor 1 Regulates Stem Cell Features of Pancreatic Cancer Cells, Independently of the PAF1 Complex, via Interactions With PHF5A and DDX3.

Background & Aims: It is not clear how pancreatic cancer stem cells (CSCs) are regulated, resulting in ineffective treatments for pancreatic cancer. PAF1, a RNA polymerase II-associated factor 1 complex (PAF1C) component, maintains pluripotency of stem cells, by unclear mechanisms, and is a marker of CSCs. We investigated mechanisms by which PAF1 maintains CSCs and contributes to development of pancreatic tumors.

MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3).

Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR-1253, a brain-enriched microRNA that regulates bone morphogenic proteins during cerebellar development.

Role of protein arginine methyltransferase 5 in group 3 (MYC-driven) Medulloblastoma.

Background: MYC amplification or overexpression is common in Group 3 medulloblastoma and is associated with the worst prognosis. Recently, protein arginine methyl transferase (PRMT) 5 expression has been closely associated with aberrant MYC function in various cancers, including brain tumors such as glioblastoma. However, the role of PRMT5 and its association with MYC in medulloblastoma have not been explored.

Disruption of C1galt1 Gene Promotes Development and Metastasis of Pancreatic Adenocarcinomas in Mice.

Background & Aims: Pancreatic ductal adenocarcinomas (PDACs) produce higher levels of truncated O-glycan structures (such as Tn and sTn) than normal pancreata. Dysregulated activity of core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) leads to increased expression of these truncated O-glycans. We investigated whether and how truncated O-glycans contributes to the development and progression of PDAC using mice with disruption of C1galt1.

Morin attenuates diethylnitrosamine-induced rat liver fibrosis and hepatic stellate cell activation by co-ordinated regulation of Hippo/Yap and TGF-β1/Smad signaling.

Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-β1 (TGF-β1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-β1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/β-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-β1/Smad pathways was not determined.

Morin impedes Yap nuclear translocation and fosters apoptosis through suppression of Wnt/β-catenin and NF-κB signaling in Mst1 overexpressed HepG2 cells.

Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells.

Morin, a dietary flavonoid, exhibits anti-fibrotic effect and induces apoptosis of activated hepatic stellate cells by suppressing canonical NF-κB signaling.

In experimental liver fibrosis, activated hepatic stellate cells (HSCs) play a central role and thus, induction of apoptosis of activated HSCs is a promising therapeutic strategy for liver fibrosis. The present study was designed to elucidate the molecular mechanisms of the pro-apoptotic effects of morin, a dietary flavonoid, in vitro and in vivo. Culture-activated human HSCs (LX-2 cells) were treated with morin (50 μM) for 24 and 48 h, and the mechanism of cell death induced by morin was evaluated.

Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling.

The anti-fibrotic effect of morin was examined in LX-2 cells (culture-activated human hepatic stellate cells) and in diethylnitrosamine induced rat model of liver fibrosis. The in vitro study was designed to determine whether morin affects the survival of cultured LX-2 cells, while the in vivo study was designed to evaluate the antioxidant and anti-fibrotic efficacy of morin on diethylnitrosamine induced liver fibrosis in male albino Wistar rat. The activities of liver function enzymes in serum, liver lipid peroxide levels, activities of serum antioxidant enzymes and liver architecture were monitored to cast light on the antioxidant and hepatoprotective nature of morin.