ROCK signalling induced gene expression changes in mouse pancreatic ductal adenocarcinoma cells

Rath, Nicola; Kalna, Gabriela; Clark, William; Olson, Michael F.

doi:10.1038/sdata.2016.101

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Although ROCK actions on actin structures and cell morphology are well‐known (Rath & Olson, ; Julian & Olson, ), the same signaling pathway regulates gene transcription (Rajakylä & Vartiainen, ). Using RNA sequencing, expressions of 305 genes were found to be significantly ( P < 0.05) changed greater than twofold in 4HT‐treated ROCK1:ER‐expressing cells relative to GFP:ER‐expressing cells (Fig A, left), while 374 genes were significantly changed in ROCK2:ER versus GFP:ER‐expressing cells (Fig A, right), of which 285 were common changes (Fig B) (Rath et al , ). The greatest significantly increased fold‐changes were Mmp10 and Mmp13 , prostaglandin‐endoperoxidase synthase 2 ( Ptgs2 also known as Cox2 ), and Tenascin‐C ( Tnc ) (Fig A and ).…”

Section: Resultsmentioning

confidence: 97%

“…Unprocessed RNA sequencing reads have been deposited as fastq files at the National Center for Biotechnology Information (NCBI) Sequence Reads Archive (SRA) with the reference SRP081135 (https://www.ncbi.nlm.nih.gov/sra/?term=srp081135) (Rath et al , ). In addition, a project overview has been submitted as the BioProject reference PRJNA327913 (http://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA327913) with a description of the BioSample reference SAMN05361890 (http://www.ncbi.nlm.nih.gov/biosample/?term=SAMN05361890).…”

Section: For More Informationmentioning

confidence: 99%

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ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth

et al. 2016

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Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death; identifying PDAC enablers may reveal potential therapeutic targets. Expression of the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human and mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression in human patients, or conditional ROCK2 activation in a Kras G12D/p53 R172H mouse PDAC model, was associated with reduced survival. Conditional ROCK1 or ROCK2 activation promoted invasive growth of mouse PDAC cells into three‐dimensional collagen matrices by increasing matrix remodeling activities. RNA sequencing revealed a coordinated program of ROCK‐induced genes that facilitate extracellular matrix remodeling, with greatest fold‐changes for matrix metalloproteinases (MMPs) Mmp10 and Mmp13. MMP inhibition not only decreased collagen degradation and invasion, but also reduced proliferation in three‐dimensional contexts. Treatment of Kras G12D/p53 R172H PDAC mice with a ROCK inhibitor prolonged survival, which was associated with increased tumor‐associated collagen. These findings reveal an ancillary role for increased ROCK signaling in pancreatic cancer progression to promote extracellular matrix remodeling that facilitates proliferation and invasive tumor growth.

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Section: Resultsmentioning

confidence: 97%

Section: For More Informationmentioning

confidence: 99%

ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth

et al. 2016

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“…The results of the expression of RhoC and ROCK proteins shown by Western blot showed that RhoC silencing decreased ROCK protein expression, which is consistent with the finding of Rong et al who showed that the downstream effector molecule of RhoC is ROCK. Some studies have shown that RhoC activates ROCK by binding with ROCK and then phosphorylates the myosin light chain, participates in cell aggregation and fiber contraction, and promotes cell metastasis and infiltration …”

Section: Discussionmentioning

confidence: 99%

“…Some studies have shown that RhoC activates ROCK by binding with ROCK and then phosphorylates the myosin light chain, participates in cell aggregation and fiber contraction, and promotes cell metastasis and infiltration. 23 The MAPK signaling pathway exists widely in cells and is involved in many biological processes, such as cell growth, development, division, differentiation, and apoptosis. This pathway is also closely associated with the development and progression of multiple malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

Effects of RhoC downregulation on the angiogenesis characteristics of myeloma vascular endothelial cells

et al. 2019

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Background Tumor angiogenesis plays an important role in disease progression, and RhoC has been previously found to be expressed in vascular endothelial cells (VECs); however, its role in tumor angiogenesis requires clarification. This study aimed to explore the effects of RhoC downregulation on the cytoskeleton, pseudopod formation, migration ability, and canalization capacity of myeloma vascular endothelial cells (MVECs) in vitro. Materials and methods The expression of RhoC in MVECs and human umbilical vein endothelial cells (HUVECs) was knocked down by shRNA, and the expression levels of RhoC mRNA were detected by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The cytoskeletal changes and pseudopods were observed by laser scanning confocal and scanning electron microscopy; VECs were incubated in two‐dimensional Matrigel and three‐dimensional microcarriers to observe tube‐like structures and budding status, respectively. The protein expression of RhoC, phosphorylation of mitogen‐activated protein kinase (p‐MAPK), and Rho‐associated coiled‐coil kinase (ROCK) was determined by Western blotting. The expression of RhoC in VECs was downregulated by RhoC shRNA, thereby decreasing the number of pseudopods, two‐dimensional tube‐like structures, and buds. Results When RhoC was downregulated, the expression levels of ROCK and phosphorylation of MAPK were both decreased ( P < 0.05). Moreover, the expression levels of RhoC and phosphorylation of MAPK and three‐dimensional budding numbers were higher in MVECs than in HUVECs ( P < 0.05). The downregulation of RhoC expression in MVECs and HUVECs inhibited pseudopod formation, migration, canalization ability, and angiogenesis ( P < 0.05). Conclusion Our data indicated that MVECs and HUVECs were well suited for angiogenesis research, but the former cell type was shown to be more advantageous in terms of budding numbers. RhoC plays a pivotal role in MVECs angiogenesis, and the downregulation of RhoC expression could inhibit angiogenesis via the RhoC/MAPK and RhoC/ROCK signaling pathways.

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“…RNA-Sequence analysis and alignment was carried out as described in reference 12 . Quality control checks of raw RNA-Seq data files were done with fastqc v0.10.1 ( http://www.bioinformatics.babraham.ac.uk/projects/fastqc/ ) and fastq_screen v0.4.2 ( http://www.bioinformatics.babraham.ac.uk/projects/fastq_screen/ ).…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic profiling of human breast and melanoma cells selected by migration through narrow constraints

et al. 2017

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The metastatic spread of cancer cells is a step-wise process that starts with dissociation from primary tumours and local invasion of adjacent tissues. The ability to invade local tissues is the product of several processes, including degradation of extracellular matrices (ECM) and movement of tumour cells through physically-restricting gaps. To identify properties contributing to tumour cells squeezing through narrow gaps, invasive MDA-MB-231 human breast cancer and MDA-MB-435 human melanoma cells were subjected to three successive rounds of selection using cell culture inserts with highly constraining 3 μm pores. For comparison purposes, flow cytometry was also employed to enrich for small diameter MDA-MB-231 cells. RNA-Sequencing (RNA-seq) using the Illumina NextSeq 500 platform was undertaken to characterize how gene expression differed between parental, invasive pore selected or small diameter cells. Gene expression results obtained by RNA-seq were validated by comparing with RT-qPCR. Transcriptomic data generated could be used to determine how alterations that enable cell passage through narrow spaces contribute to local invasion and metastasis.

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ROCK signalling induced gene expression changes in mouse pancreatic ductal adenocarcinoma cells

Cited by 7 publications

References 18 publications

ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth

ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth

Effects of RhoC downregulation on the angiogenesis characteristics of myeloma vascular endothelial cells

Transcriptomic profiling of human breast and melanoma cells selected by migration through narrow constraints

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