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Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer

ABSTRACT: Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer

PROVIDER: PRJNA607204 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11098948.fastq.gz	Fastqsanger.gz
	SRR11098949.fastq.gz	Fastqsanger.gz
	SRR11098950.fastq.gz	Fastqsanger.gz
	SRR11098951.fastq.gz	Fastqsanger.gz
	SRR11098952.fastq.gz	Fastqsanger.gz

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Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer [Tissue]

Project description:Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer [Tissue]

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Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer [Cells]

Project description:Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer [Cells]

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Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer [Tissue]

Project description:Analysis of colorectal primary tumors (pTU) and liver metastases (LM) tissue samples from patients and identify corresponding gene expression signatures

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Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer [Cells]

Project description:Analysis of primary fibroblasts isolated from human colorectal primary tumors(CAFs) and liver metastases(MAFs) and identify corresponding gene expression signatures

2020-05-01 | GSE145428 | GEO

Reducing metastases stiffness by targeting fibroblasts improves therapeutic outcome in colorectal cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-05-01 | GSE145432 | GEO

Combined Calorie and Protein Restriction in Healthy Kidney Donors Improves Kidney Outcome in Donors and Kidney Transplant Recipients

Project description:A preoperative short-term diet combining calorie and protein restriction diet given during five days before kidney donation and transplantation improves kidney outcome in live kidney donors and kidney transplant recipients, which shows that the benefits of dietary restriction on stress resistance can be induced rapidly in humans, and may be used for clinically relevant endpoints.

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Tumor matrix stiffness induces CCN1/CYR61 upregulation of N-Cadherin to promote cancer cell trans-endothelial migration and metastasis

Project description:Tumor progression is often accompanied with increased extracellular matrix stiffness, but how this affects endothelial cells (ECs) is largely unknown. We used mass spectrometry to analyse the proteomic changes of primary human ECs cultured on physiological or tumor stiffness and found that CCN1/CYR61 is highly induced by tumor stiffness. Knock out of Ccn1 in the vasculature of Ccn1loxP/loxP mice by administrating a soluble form of Cre shows that fewer of the treated mice harbour circulating tumor cells and lung metastases, without affecting primary tumor growth, using the B16F10 syngeneic mouse melanoma model This demonstrates that CCN1 loss in the host impairs cancer metastasis and we dissected the molecular mechanism in vitro. Stiffness-induced CCN1 acts via (integrin αvβ3), FAK, beta-catenin signalling to increase N-Cadherin expression in ECs, which, in turn, leads to an elevated adhesion of cancer cells to ECs via N-Cadherin homophilic interactions.

2017-07-07 | PXD003316 | Pride

Key role for Rac in the early transcriptional response to ECM stiffness and the stiffness-dependent repression of ATF3

Project description:The Rho family GTPases, Rac and Rho, play critical roles in transmitting mechanical information contained within the extracellular matrix (ECM) to the cell. Rac and Rho have well described roles in regulating stiffness-dependent actin remodeling, proliferation and motility. However, much less is known about the relative roles of these GTPases in stiffness-dependent transcription, particularly at the genome-wide level. Here, we selectively inhibited Rac and Rho in mouse embryonic fibroblasts cultured on deformable substrata and used RNA sequencing to elucidate and compare the contribution of these GTPases to the early transcriptional response to ECM stiffness. Surprisingly, we found that the stiffness-dependent activation of Rac is dominant over Rho in the initial transcriptional response to ECM stiffness. We also identified Activating Transcription Factor 3 (ATF3) as a major target of stiffness/Rac-mediated signaling and show that ATF3 repression by ECM stiffness helps to explain how the stiffness-dependent activation of Rac results in the induction of cyclin D1.

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A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer

Project description:Intratumor heterogeneity associates with poor patient outcome. Stromal stiffening also accompanies cancer. Whether cancers demonstrate stiffness heterogeneity, and if this is linked to tumor cell heterogeneity remains unclear. We developed a method to measure the stiffness heterogeneity in human breast tumors that quantifies the stromal stiffness each cell experiences and permits visual registration with biomarkers of tumor progression. We present Spatially Transformed Inferential Force Map (STIFMap) which exploits computer vision to precisely automate atomic force microscopy (AFM) indentation combined with a trained convolutional neural network to predict stromal elasticity with micron-resolution using collagen morphological features and ground truth AFM data. We registered high-elasticity regions within human breast tumors colocalizing with markers of mechanical activation and an epithelial-to-mesenchymal transition (EMT). The findings highlight the utility of STIFMaps to assess mechanical heterogeneity of human tumors across length scales from single cells to whole tissues and implicates stromal stiffness in tumor cell heterogeneity.

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Identification of candidate genes affecting juvenile wood stiffness in Pinus radiata

Project description:Wood stiffness is the most important wood quality trait of forest trees for structural timber production. We investigated genes differentially transcribed in radiate pine trees with distinct wood stiffness using bulked segregant analysis (BSA) and cDNA microarrays. Transcript accumulation in earlywood (EW) and latewood (LW) of high (HS) and low stiffness (LS) trees in two progeny trials was compared. Radiata pine trees used for microarray experiment were selected from two progeny trials planted at Flynn and Kromelite, Australia. Based on the IML-based MOE measurement, five families with highest and lowest MOE each were selected from each trial, which represented two segregant populations with contrasting wood stiffness. Two individuals from each selected family were further sampled. Developing xylem tissues of selected trees in Flynn trial were sampled in spring (October) and autumn (April), representing earlywood (EW) and latewood (LW) of juvenile aged trees, respectively. Collection of xylem tissues from Kromelite trial was arranged in summer (late November) when latewood (LW) was formed. The xylem tissues were scraped at breast height with a sharp chisel after the bark was removed. In Flynn trial EW and LW tissues were collected from the same sampled trees on opposite sides of the trunk. Transcript accumulation was compared in trees with highest (HS) and lowest stiffness (LS) using xylem samples from Flynn collected in spring (EW) and autumn (LW), as well as Kromelite in summer (LW), respectively. Bulked segregant analysis (BSA) was used for the experiment design. Total RNA samples extracted from the five trees with HS were pooled at equal amount, and compared to the bulked five individuals with LS. This pooling strategy can partly minimize the genetic variation among different genotypes. Dye swaps were applied in each biological replicate.

2011-06-01 | E-GEOD-23020 | biostudies-arrayexpress

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