Heat Dissipation Mechanisms in Hybrid Superconductor-Semiconductor Devices Revealed by Joule Spectroscopy.

Understanding heating and cooling mechanisms in mesoscopic superconductor-semiconductor devices is crucial for their application in quantum technologies. Owing to their poor thermal conductivity, heating effects can drive superconducting-to-normal transitions even at low bias, observed as sharp conductance dips through the loss of Andreev excess currents. Tracking such dips across magnetic field, cryostat temperature, and applied microwave power allows us to uncover cooling bottlenecks in different parts of a device.

Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells.

Background & Aims: Metallothionein-3 (hMT3) is a structurally unique member of the metallothioneins family of low-mass cysteine-rich proteins. hMT3 has poorly characterized functions, and its importance for hepatocellular carcinoma (HCC) cells has not yet been elucidated. Therefore, we investigated the molecular mechanisms driven by hMT3 with a special emphasis on susceptibility to sorafenib.

A complex of cadherin 17 with desmocollin 1 and p120-catenin regulates colorectal cancer migration and invasion according to the cell phenotype.

Background: Cadherin-17 (CDH17), a marker of differentiation in intestinal cells, binds and activates α2β1 integrin to promote cell adhesion and proliferation in colorectal cancer (CRC) metastasis. Furthermore, CDH17 associates with p120- and β-catenin in a manner yet to be fully elucidated. In this report, we explored the molecular mediators involved in this association, their contribution to CRC dissemination and potential therapeutic implications.

Integrated meta-analysis of colorectal cancer public proteomic datasets for biomarker discovery and validation.

The cancer biomarker field has been an object of thorough investigation in the last decades. Despite this, colorectal cancer (CRC) heterogeneity makes it challenging to identify and validate effective prognostic biomarkers for patient classification according to outcome and treatment response. Although a massive amount of proteomics data has been deposited in public data repositories, this rich source of information is vastly underused.

Schnurri-3 drives tumor growth and invasion in cancer cells expressing interleukin-13 receptor alpha 2.

Interleukin 13 receptor alpha 2 (IL13Rα2) is a relevant therapeutic target in glioblastoma (GBM) and other tumors associated with tumor growth and invasion. In a previous study, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) is a key mediator of the IL-13/IL13Rα2 signaling pathway. PTP1B regulates cancer cell invasion through Src activation.

Proteomic profiling and network biology of colorectal cancer liver metastasis.

Introduction: Tissue-based proteomic studies of colorectal cancer (CRC) metastasis have delivered fragmented results, with very few therapeutic targets and prognostic biomarkers moving beyond the discovery phase. This situation is likely due to the difficulties in obtaining and analyzing large numbers of patient-derived metastatic samples, the own heterogeneity of CRC, and technical limitations in proteomics discovery. As an alternative, metastatic CRC cell lines provide a flexible framework to investigate the underlying mechanisms and network biology of metastasis for target discovery.

Interleukin 13 receptor alpha 2 (IL13Rα2): Expression, signaling pathways and therapeutic applications in cancer.

Interleukin 13 receptor alpha 2 (IL13Rα2) is increasingly recognized as a relevant player in cancer invasion and metastasis. Despite being initially considered a decoy receptor for dampening the levels of interleukin 13 (IL-13) in diverse inflammatory conditions, accumulating evidences in the last decades indicate the capacity of IL13Rα2 for mediating IL-13 signaling in cancer cells. The biological reasons behind the expression of this receptor with such extremely high affinity for IL-13 in cancer cells remain unclear.

Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis.

Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows.

Inhibition of Liver Metastasis in Colorectal Cancer by Targeting IL-13/IL13Rα2 Binding Site with Specific Monoclonal Antibodies.

Background: IL13Rα2 is reportedly a promising therapeutic target in different cancers. Still, no specific antagonists have reached the clinics yet. We investigated the use of a IL-13/IL13Rα2 binding motif, called D1, as a new target for the development of therapeutic monoclonal antibodies (mAbs) for colorectal cancer (CRC) metastasis.

Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma.

Metallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance.

SOSTDC1 promotes invasion and liver metastasis in colorectal cancer via interaction with ALCAM/CD166.

The mechanistic basis of liver metastasis in colorectal cancer remains poorly understood. We previously reported that the sclerostin domain containing-1 (SOSTDC1) protein is overexpressed in the secretome of metastatic colorectal cancer cells and can inhibit liver homing. Here, we investigated the mechanisms of SOSTDC1 for promoting invasiveness and progression of colorectal cancer liver metastasis.

Potential Role of Circulating Endoglin in Hypertension via the Upregulated Expression of BMP4.

Endoglin is a membrane glycoprotein primarily expressed by the vascular endothelium and involved in cardiovascular diseases. Upon the proteolytic processing of the membrane-bound protein, a circulating form of endoglin (soluble endoglin, sEng) can be released, and high levels of sEng have been observed in several endothelial-related pathological conditions, where it appears to contribute to endothelial dysfunction. Preeclampsia is a multisystem disorder of high prevalence in pregnant women characterized by the onset of high blood pressure and associated with increased levels of sEng.

Protein Tyrosine Phosphatase-1B Inhibition Disrupts IL13Rα2-Promoted Invasion and Metastasis in Cancer Cells.

Interleukin 13 receptor alpha 2 subunit (IL13Rα2) is overexpressed in glioblastoma (GBM), metastatic colorectal cancer (CRC) and ovarian cancer (OC). Here, we investigated the IL13Rα2 interactome searching for novel targets in cancer invasion and metastasis. The interactome of IL13Rα2 was determined in GBM by using a proteomic analysis and then validated in CRC and OC.

Identification and Validation of Stage-Associated Serum Biomarkers in Colorectal Cancer Using MS-Based Procedures.

Purpose: Successful prevention of colorectal cancer (CRC) would benefit from a rapid serum screening for early detection. Here, a novel strategy for CRC biomarker discovery and validation exclusively based on MS procedures is reported.

Experimental Design: Identification of CRC serum biomarkers is initially made using label-free quantification on pooled serum samples from different CRC stages followed by two consecutive steps of targeted parallel reaction monitoring assays in different serum cohorts.

Beyond N-Cadherin, Relevance of Cadherins 5, 6 and 17 in Cancer Progression and Metastasis.

Cell-cell adhesion molecules (cadherins) and cell-extracellular matrix adhesion proteins (integrins) play a critical role in the regulation of cancer invasion and metastasis. Although significant progress has been made in the characterization of multiple members of the cadherin superfamily, most of the published work continues to focus in the switch E-/N-cadherin and its role in the epithelial-mesenchymal transition. Here, we will discuss the structural and functional properties of a subset of cadherins (cadherin 17, cadherin 5 and cadherin 6) that have an RGD motif in the extracellular domains.

c-Met Signaling Is Essential for Mouse Adult Liver Progenitor Cells Expansion After Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition and Regulates Cell Phenotypic Switch.

Adult hepatic progenitor cells (HPCs)/oval cells are bipotential progenitors that participate in liver repair responses upon chronic injury. Recent findings highlight HPCs plasticity and importance of the HPCs niche signals to determine their fate during the regenerative process, favoring either fibrogenesis or damage resolution. Transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) are among the key signals involved in liver regeneration and as component of HPCs niche regulates HPCs biology.

PAUF/ZG16B promotes colorectal cancer progression through alterations of the mitotic functions and the Wnt/β-catenin pathway.

Pancreatic adenocarcinoma upregulated factor (PAUF), also known as ZG16B, was previously found in the secretome of metastatic colorectal cancer cells. Here, we demonstrated the presence of PAUF at the intracellular level and its multiple effects on cancer progression. An initial decline of PAUF expression was observed at early stages of colorectal cancer followed by an increase at the metastatic site.

PIM kinases mediate resistance of glioblastoma cells to TRAIL by a p62/SQSTM1-dependent mechanism.

Glioblastoma (GBM) is the most common and aggressive brain tumor and is associated with poor prognosis. GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge. PIM kinases are serine/threonine kinases that promote cell survival and proliferation and are highly expressed in different tumors.

An IL13Rα2 peptide exhibits therapeutic activity against metastatic colorectal cancer.

Background: Interleukin 13 receptor α2 (IL13Rα2) is overexpressed in metastatic colorectal cancer. Here, we have developed novel strategies to block IL-13 binding to IL13Rα2 in order to reduce metastatic spread.

Methods: Synthetic IL13Rα2 D1 peptide (GSETWKTIITKN) was tested for the inhibition of IL-13 binding to IL13Rα2 using ELISA and different cellular assays.

RGD cadherins and α2β1 integrin in cancer metastasis: A dangerous liaison.

We propose a new cadherin family classification comprising epithelial cadherins (cadherin 17 [CDH17], cadherin 16, VE-cadherin, cadherin 6 and cadherin 20) containing RGD motifs within their sequences. Expression of some RGD cadherins is associated with aggressive forms of cancer during the late stages of metastasis, and CDH17 and VE-cadherin have emerged as critical actors in cancer metastasis. After binding to α2β1 integrin, these cadherins promote integrin β1 activation, and thereby cell adhesion, invasion and proliferation, in liver and lung metastasis.

Proteomic Characterization of Transcription and Splicing Factors Associated with a Metastatic Phenotype in Colorectal Cancer.

We investigated new transcription and splicing factors associated with the metastatic phenotype in colorectal cancer. A concatenated tandem array of consensus transcription factor (TF)-response elements was used to pull down nuclear extracts in two different pairs of colorectal cancer cells, KM12SM/KM12C and SW620/480, genetically related but differing in metastatic ability. Proteins were analyzed by label-free LC-MS and quantified with MaxLFQ.

Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach.

The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments.

Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis.

New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAb). Cadherin 17 (CDH17) fragments and peptides were prepared and used for immunization and antibody development.

Mapping the Spatial Proteome of Metastatic Cells in Colorectal Cancer.

Colorectal cancer (CRC) is the second deadliest cancer worldwide. Here, we aimed to study metastasis mechanisms using spatial proteomics in the KM12 cell model. Cells were SILAC-labeled and fractionated into five subcellular fractions corresponding to: cytoplasm, plasma, mitochondria and ER/golgi membranes, nuclear, chromatin-bound and cytoskeletal proteins and analyzed with high resolution mass spectrometry.

Combined miRNA profiling and proteomics demonstrates that different miRNAs target a common set of proteins to promote colorectal cancer metastasis.

The process of liver colonization in colorectal cancer remains poorly characterized. Here, we addressed the role of microRNA (miRNA) dysregulation in metastasis. We first compared miRNA expression profiles between colorectal cancer cell lines with different metastatic properties and then identified target proteins of the dysregulated miRNAs to establish their functions and prognostic value.