Cancers, Vol. 11, Pages 1959: Negative Control of Cell Migration by Rac1b in Highly Metastatic Pancreatic Cancer Cells Is Mediated by Sequential Induction of Nonactivated Smad3 and Biglycan

Cancers, Vol. 11, Pages 1959: Negative Control of Cell Migration by Rac1b in Highly Metastatic Pancreatic Cancer Cells Is Mediated by Sequential Induction of Nonactivated Smad3 and Biglycan Cancers doi: 10.3390/cancers11121959 Authors: Hannah Otterbein Hendrik Lehnert Hendrik Ungefroren Expression of the small GTPase, Ras-related C3 botulinum toxin substrate 1B (RAC1B), a RAC1-related member of the Rho GTPase family, in tumor tissues of pancreatic ductal adenocarcinoma (PDAC) has been shown previously to correlate positively with patient survival, but the underlying mechanism(s) and the target genes involved have remained elusive. Screening of a panel of established PDAC-derived cell lines by immunoblotting indicated that both RAC1B and Mothers against decapentaplegic homolog 3 (SMAD3) were more abundantly expressed in poorly metastatic and well-differentiated lines as opposed to highly metastatic, poorly differentiated ones. Both siRNA-mediated RAC1B knockdown in the transforming growth factor (TGF)-β-sensitive PDAC-derived cell lines, Panc1 and PaCa3, or CRISPR/Cas-mediated knockout of exon 3b of RAC1 in Panc1 cells resulted in a dramatic decrease in the expression of SMAD3. Unexpectedly, the knockdown of SMAD3 reproduced the promigratory activity of a RAC1B knockdown in Panc1 and PaCa3, but not in TGF-β-resistant BxPC3 and Capan1 cells, while forced expression of SMAD3 alone was able to mimic the antimigratory effect of ectopic RAC1B overexpre...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
ConclusionsThe findings of this study provide evidence that FUT8 plays a pivotal role in PDAC invasion and metastasis and might be a therapeutic target for this disease.
Source: Surgery Today - Category: Surgery Source Type: research
I. E. Bruce Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to standard treatments leading to poor patient survival. The expression of plasma membrane calcium ATPase-4 (PMCA4) is reported to modulate key cancer hallmarks including cell migration, growth, and apoptotic resistance. Data-mining revealed that PMCA4 was over-expressed in pancreatic ductal adenocarcinoma (PDAC) tumors which correlated with poor patient survival. Western blot and RT-qPCR revealed that MIA PaCa-2 cells almost exclusively express PMCA4 making these a suitable cellular model of PDAC with poor patient survival. Knockdown of PMCA4 in ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSIONS: Thus, these results indicated that SNHG14 expression acts as a prognostic maker for PDAC and potential target of PDAC treatment. PMID: 31929143 [PubMed - as supplied by publisher]
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
Authors: Shang M, Zhang L, Chen X, Zheng S Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies without effective screening strategy during the early stage. Therefore, a novel screening panel was identified based on potential biomarkers associated with PDAC using the gene expression profile. The dataset GSE15471, which was downloaded from the Gene Expression Omnibus (GEO) database, included matching pairs of normal and tumor tissue samples from the resected pancreas of 39 pancreatic cancer patients. We used the online tool GEO2R to screen and pick out the differentially expressed ...
Source: Discovery Medicine - Category: Research Tags: Discov Med Source Type: research
Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal a...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
Conditions:   Metastatic Pancreatic Cancer;   Metastatic Pancreatic Adenocarcinoma Interventions:   Drug: Dose;   Drug: Dose -SM-88;   Drug: Dose -mFOLFIRINOX Sponsor:   Pancreatic Cancer Action Network Not yet recruiting
Source: - Category: Research Source Type: clinical trials
Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis, mainly because only 15–20% of all patients present with resectable tumor stages at the time of diagnosis. Due to locally extended tumor growth or distant metastases upfront resection is not reasonable in the majority of patients. Considerably, PDAC will be the 2nd most frequent cause of cancer-related deaths within the next 10 years for both men and women. While there is currently no convincing evidence for the use of neoadjuvant therapy in resectable PDAC, there are controversial results from studies investigating neoadjuvant treatment concepts in...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Contributor : Reuben MoncadaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSingle-cell RNA sequencing (scRNA-seq) enables the systematic identification of cell populations in a tissue, but characterizing their spatial organization remains challenging. We combine a microarray-based spatial transcriptomics method that reveals spatial patterns of gene expression using an array of spots, each capturing the transcriptomes of multiple adjacent cells, with scRNA-Seq generated from the same sample. To annotate the precise cellular composition of distinct tissue regions, we introduce a method...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
In this study, we found that higher expression of four-and-a-half LIM domains 3 (FHL3) predicted poor prognosis in PDAC. The decreasing of FHL3 changed the EMT phenotype by blocking the TGFβ/Atk/GSK3β/ubiquitin pathways. Interestingly, the GSK3β inhibitor could abrogate the role of FHL3 in the regulation of snail1 and twist1 expression, which implied that GSK3β plays a pivotal role in the FHL3-mediated EMT process. Furthermore, we found that FHL3 can directly bind to GSK3β, which weakened the interaction between GSK3β and snail1/twist1. We also found that the LIM-3 domain of FHL3 was required ...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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