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Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [SW480 and SW837]

ABSTRACT: Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [SW480 and SW837]

PROVIDER: PRJNA1195348 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR31639779.fastq.gz	Fastqsanger.gz
	SRR31639780.fastq.gz	Fastqsanger.gz
	SRR31639781.fastq.gz	Fastqsanger.gz
	SRR31639782.fastq.gz	Fastqsanger.gz

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Similar Datasets

Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [SW480 and SW837]

Project description:Colorectal cancer (CRC) responses to mutant-selective KRAS inhibitors remain modest, with stable disease and rapid recurrence as the most common outcomes. The molecular mechanisms enabling CRC cells to tolerate KRAS inhibition and ultimately develop resistance remain poorly understood. Here, we investigated early transcriptional and proteomic responses to KRAS silencing in 3D CRC cell line spheroid models, aiming to identify pathways associated with sensitivity or resistance to KRAS blockade. Cell lines were stratified into KRAS silencing-sensitive (HCT116 and SW480) and -resistant (LS174T and SW837) groups based on spheroid growth, cell cycle progression, and apoptosis induction. Transcriptional profiling revealed the unfolded protein response (UPR) and WNT/β-catenin signaling as pathways specifically upregulated in KRAS silencing-sensitive cells and downregulated in resistant cells. Proteomic analysis of membrane-enriched fractions further supported UPR deregulation, showing a pronounced downregulation of translation-related proteins in sensitive cells. Functional assays validated that the sensitive cell line HCT116 exhibits reduced protein aggregation and lower translational capacity upon KRAS knockdown, consistent with UPR activation. Pharmacological inhibition of IRE1α-mediated UPR signaling did not revert KRAS silencing-induced cell cycle arrest or apoptosis in this cell line. Collectively, our results highlight the UPR activation as an early adaptive response of KRAS-dependent CRC cells tolerant to KRAS silencing.

2024-12-12 | GSE283752 | GEO

Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [LS174T]

2024-02-06 | GSE254833 | GEO

Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [HCT116]

2024-02-06 | GSE254832 | GEO

Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [HCT116]

Project description:Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [HCT116]

| PRJNA1072042 | ENA

Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [LS174T]

Project description:Differential unfolded protein response regulation in KRAS silencing sensitive versus innately resistant colorectal cancer cells [LS174T]

| PRJNA1072041 | ENA

KRAS inhibition impacts chromatin organization and transcriptional performance in colorectal cancer cells [SW480 RNA-seq]

Project description:Preclinical and clinical data revealed that targeting KRAS mutant tumors is more challenging than expected. While initially sensitive to the treatment, cancer cells have the capability to rapidly bypass dependence on this oncogene to acquire a drug-tolerant phenotype. Gaining a comprehensive understanding of the mechanisms underlying the transition from a drug-sensitive to a drug-tolerant state holds the key to invaluable insights. Such insights will inform the development of therapeutic strategies aimed at disrupting intrinsic or adaptive resilience, ultimately enhancing therapeutic outcomes. Building upon this rationale, we established three-dimensional culture models of mutant KRAS CRC cell lines with distinct KRAS dependencies to investigate the cellular response to KRAS silencing. Our approach revealed a unique response in KRAS-dependent cells, characterized by G0/G1 cell cycle arrest and entry into a quiescent-like state. Proteomics analysis identified nucleosome assembly, regulation of gene expression, mRNA splicing, and mRNA processing as the top biologic processes specifically up-regulated in KRAS-dependent CRC cell lines upon KRAS silencing. Additionally, alterations in histone 3 post-translational modifications and chromatin compaction were also observed, along with enhanced transcriptional performance revealed by longitudinal RNA-Seq analysis. Our discoveries substantiate the existence of an epigenetic mechanism responsible for inducing tolerance to KRAS loss. This mechanism relies on both chromatin reorganization and transcriptional upregulation, illuminating the cancer cells' remarkable capacity to swiftly adapt, survive, and sustain malignancy even in the absence of oncogenic KRAS.

2023-12-15 | GSE250118 | GEO

The RALA pathway can maintain the proliferation of KRAS- and BRAF-mutated cancer cells

Project description:By silencing of RALA, a downstream member of the RAS signal transduction pathway, we aimed to determine whether genes downstream of a mutated KRAS (codon 12 or 13) or a mutated BRAF can have significant functions in colorectal cancer carcinogenesis. RALA was silenced in three colorectal cancer cell lines (SW480, HCT116 and HT29). Effects were normalized to mock-transfected cells and the effects of scramble siRNA were excluded. SW480, HCT116 and HT29 cell lines were treated with the PI3K inhibitor LY294002 or DMSO.

2015-06-20 | E-GEOD-39857 | biostudies-arrayexpress

Next Generation Sequencing Facilitates Quantitative Analysis of SW480 cells and HPSE-knockdown SW480 cells Transcriptomes

Project description:Heparanase (HPSE), the only known mammalian endoglycosidase responsible for heparan sulfate cleavage, is a multi-faceted protein affecting multiple malignant behaviors in cancer cells. The goals of this study are to compare the mRNA transcriptome differences between SW480 cells and HPSE-knockdown SW480 cells. Methods: mRNA profiles of SW480 cells and HPSE-knockdown SW480 cells were generated by deep sequencing, in triplicate, using Illumina.

2019-02-14 | GSE126504 | GEO

KRAS inhibition impacts chromatin organization and transcriptional performance in colorectal cancer cells [SW480 RNA-seq]

Project description:KRAS inhibition impacts chromatin organization and transcriptional performance in colorectal cancer cells [SW480 RNA-seq]

| PRJNA1052056 | ENA

Ezrin knockdown in SW480

Project description:Analysis of SW480 cells following knockdown of Ezrin using RNAi. Ezrin is a protein that regulate the organization of cytoskeleton. Ezrin KD SW480 was used to study the role of ezrin in colon cancer. Keywords: ezrin, colon cancer, migration

2008-04-29 | GSE11279 | GEO

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