Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer

ABSTRACT: The assessment of global changes in fibrillar collagens and to the larger extent e.g., ECM induced upon inhibitor treatment has largely been lacking for the currently available LOX family inhibitors. We therefore undertook a quantitative pharmacodynamics approach to characterize the global alterations in the ECM composition and organization upon targeting LOX with LXG6403 using state-of-the-art ECM-targeted proteomics coupled with mass spectrometry imaging

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Breast

DISEASE(S): Breast Cancer

SUBMITTER: Harrison Taylor

LAB HEAD: Peggi Angel

PROVIDER: PXD052642 | Pride | 2025-12-01

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	6403_617.d.zip	Other
	6403_646.d.zip	Other
	6403_653.d.zip	Other
	C3_Combo_624.d.zip	Other
	C3_Combo_642.d.zip	Other

Items per page:

1 - 5 of 13

Publications

A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer.

Cetin Metin M Saatci Ozge O Rezaeian Abdol-Hossein AH Rao Chintada Nageswara CN Beneker Chad C Sreenivas Kukkamudi K Taylor Harrison H Pederson Breanna B Chatzistamou Ioulia I Buckley Brian B Lessner Susan S Angel Peggi P McInnes Campbell C Sahin Ozgur O

Cell chemical biology 20240722 11

Lysyl oxidase (LOX) is upregulated in highly stiff aggressive tumors, correlating with metastasis, resistance, and worse survival; however, there are currently no potent, safe, and orally bioavailable small molecule LOX inhibitors to treat these aggressive desmoplastic solid tumors in clinics. Here we discovered bi-thiazole derivatives as potent LOX inhibitors by robust screening of drug-like molecules combined with cell/recombinant protein-based assays. Structure-activity relationship analysis ...[more]

PMID: 39043186

Similar Datasets

A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer

Project description:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) data investigating changes in extracellular matrix/collagen architecture of mouse tumor tissue in response to LOX inhibition. Sample Key: Vehicle, Doxo (Chemotherapy drug), 6403 (LOX inhibitor), Combo (Doxo + LOX inhibitor)

2024-07-25 | PXD052657 | Pride

A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer

Project description:Raw proteomic files Metin C, Saatci O, Rezaeian A-H, Rao CN, Beneker C, Taylor H, Pederson B, Chatzistamou I, Buckley B, Lessner S, Angel P, McInnes C, Sahin O. A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer. Cell Chem Biol

2024-05-16 | MSV000094776 | MassIVE

MS imaging of tryptic peptides in mouse brain measured at 50 µm pixel size

Project description:A coronal mouse brain section that was measured at 50µm pixel size revealed detailed histological structures such as the ependyma (consisting of one to two cell layers, which was confirmed by HE staining).

2018-08-08 | PXD003172 | Pride

LOX inhibition (BAPN treatment) attenuates satellite cell differentiation

Project description:Integration of extracellular matrix (ECM)-derived cues into transcriptional programs is essential primarily in rapidly morphing environments such as regenerating tissues. Here we demonstrate that Lysyl oxidase (Lox), known for its ECM modifying activities, primarily collagen crosslinking and fibronectin matrix assembly, also directly regulates transcription factor (TF) localization. Using genetic and pharmacological strategies, we highlight a novel intracellular role for Lox in myogenic progenitors essential for muscle regeneration. We show that Lox interacts with, and directly oxidizes, Vestigial-Like 3 (Vgll3), a transcriptional co-activator acting with Mef2 and TEF TFs. This enzymatic activity is required for Vgll3 cytoplasmic to nuclear translocation in regulation of myogenic differentiation. Our work highlights a novel mechanism for TF sub-cellular localization and suggests a mechanism for integrating ECM organization with transcriptional output during myogenic differentiation. Modulating this integration mechanism could affect the balance between ECM organization and cell differentiation and serve as a basis for novel therapeutic strategies targeting fibrotic pathologies.

2020-03-17 | GSE147007 | GEO

Spatial multi-omics in skeletal muscle unravel complex myofiber architecture

Project description:Spatial distribution of metabolites and phospholipids in murine tibialis anterior (TA) muscles.

2024-09-27 | PXD048809 | Pride

Transcriptome In Vivo Analysis (TIVA) of spatially defined single cells in intact live mouse and human brain tissue

Project description:Transcriptome profiling is an indispensable tool in advancing the understanding of single cell biology, but depends upon methods capable of isolating mRNA at the spatial resolution of a single cell. Current capture methods lack sufficient spatial resolution to isolate mRNA from individual in vivo resident cells without damaging adjacent tissue. Because of this limitation, it has been difficult to assess the influence of the microenvironment on the transcriptome of individual neurons. Here, we engineered a Transcriptome In Vivo Analysis (TIVA)-tag, which upon photoactivation enables mRNA capture from single cells in live tissue. Using the TIVA-tag in combination with RNA-seq to analyze transcriptome variance among single dispersed cells and in vivo resident mouse and human neurons, we show that the tissue microenvironment shapes the transcriptomic landscape of individual cells. The TIVA methodology provides the first noninvasive approach for capturing mRNA from single cells in their natural microenvironment. Samples represent cortex and hippocampus neuron cells collected by pipette and TIVA captured.

2014-01-12 | E-GEOD-52525 | biostudies-arrayexpress

Proteomic identification of a gastric tumor ECM signature associated with cancer progression

Project description:The extracellular matrix (ECM) plays an undisputable role in tissue homeostasis and its deregulation leads to altered mechanical and biochemical cues that impact cancer development and progression. Herein, we undertook a novel approach to address the role of gastric ECM in tumorigenesis, which remained largely unexplored. By combining decellularization techniques with a high-throughput quantitative proteomics approach, we have performed an extensive characterization of human gastric mucosa, uncovering its composition and distribution among tumor, normal adjacent and normal distant mucosa. Our results revealed a common ECM signature composed of 142 proteins and indicated that gastric carcinogenesis encompasses ECM remodeling through alterations in the abundance of 24 components, mainly basement membrane proteins. Indeed, we could only identify one de novo tumor-specific protein, the collagen alpha-1(X) chain (COL10A1). Functional analysis of the data demonstrated that gastric ECM remodeling favor tumor progression by activating ECM receptors and cellular processes involved in angiogenesis and cell-extrinsic metabolic regulation. By analyzing mRNA expression in an independent GC cohort available at the TGCA, we validated the expression profile of 12 differentially expressed ECM proteins. Importantly, the expression of COL1A2, LOX and LTBP2 significantly correlated with high tumor stage, with LOX and LTBP2 further impacting patient overall survival. Our results contribute for a better understanding of GC biology and highlight the role of core ECM components in gastric carcinogenesis and their clinical relevance as biomarkers of disease prognosis.

2022-05-20 | PXD029782 | Pride

Small molecule inhibitors of lysyl oxidases synergize with 5-azacytidine to restore erythropoiesis in myeloid neoplasms

Project description:In this study, we assessed the effects of lysyl oxidase (LOX/LOXL) inhibition on the composition of extracellular matrix (ECM) produced by in vitro expanded bone marrow derived mesenchymal stromal cells (MSCs) of n=3 patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).

2023-02-17 | PXD031217 | Pride

Machine learning for grading and prognosis of esophageal dysplasia using mass spectrometry and histological imaging

Project description:Background: Barrett’s esophagus (BE) is a precursor lesion of esophageal adenocarcinoma and may progress from non-dysplastic through low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and cancer. Grading BE is of crucial prognostic value and is currently based on the subjective evaluation of biopsies. This study aims to investigate the potential of machine learning (ML) using spatially resolved molecular data from mass spectrometry imaging (MSI) and histological data from microscopic haematoxylin and eosin (H&E)-stained imaging for computer-aided diagnosis and prognosis of BE. Methods: Biopsies from 57 patients were considered, divided into non-dysplastic (n=15), LGD non-progressive (n=14), LGD progressive (n=14), and HGD (n=14). MSI experiments were conducted at 50x50 μm spatial resolution per pixel corresponding to a tile size of 96x96 pixels in the co-registered H&E images, making a total of 144,823 tiles for the whole dataset. Results: ML models were trained to distinguish epithelial tissue from stroma with area-under-the-curve (AUC) values of 0.89 (MSI) and 0.95 (H&E)) and dysplastic grade (AUC of 0.97 (MSI) and 0.85 (H&E)) on a tile level, and low-grade progressors from non-progressors on a patient level (accuracies of 0.72 (MSI) and 0.48 (H&E)). Conclusions: In summary, while the H&E-based classifier was best at distinguishing tissue types, the MSI-based model was more accurate at distinguishing dysplastic grades and patients at progression risk, which demonstrates the complementarity of both approaches.

2021-11-15 | PXD028949 | Pride

Investigation of region specific lipid alterations in symptomatic atherosclerotic plaques using mass spectrometry imaging

Project description:Atherosclerotic plaques are composed by different cell populations that interact one with each other in a complex and heterogeneous environment. Here we report a MALDI mass spectrometry imaging investigation of the lipid profile of specific plaque regions, to discriminate between symptomatic and asymptomatic atheromas. Regions were defined by histologic staining and immunofluorescence of consecutive tissue sections.

2021-09-10 | PXD023663 | Pride