scholarly journals A Cancer Cell Cluster Marked by LincRNA MEG3 Leads Pancreatic Ductal Adenocarcinoma Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hong Pan ◽  
Huanrong Diao ◽  
Wen Zhong ◽  
Taifang Wang ◽  
Ping Wen ◽  
...  
Keyword(s):  
Single Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Marker Gene ◽  
Differentially Expressed Gene ◽  
Ductal Adenocarcinoma ◽  
Multiple Cancer ◽  
Mesenchymal Transition

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with poor prognosis and rising incidence worldwide. Late detection and particularly aggressive characteristics are the major challenges that lead to therapeutic failure of this disease. A well described gene program and core regulators are yet to be discovered to drive the metastasis of the PDAC cells. As the development of single cell omics technologies including single cell RNA-sequencing (scRNA-seq), detailed characterization of the cellular composition of solid tumors and their microenvironments are well elaborated. In the current study, we accessed a recently published scRNA-seq dataset on primary and metastatic PDAC tissues and subset the tumor cells. By comparative analysis, we profiled the differentially expressed gene programs of primary and metastatic PDAC and found several long intergenic non-coding RNAs (LincRNAs) in top genes. The PDAC cancer cells showed some heterogeneity and were divided into four major subclusters based on gene profiles, one of which was mostly contributed by metastatic PDAC. Interestingly, this subcluster was remarkably marked by one of the above LincRNAs, MEG3, and exhibited significantly increased Epithelial–Mesenchymal-Transition (EMT) signatures. Ingenuity Pathway Analysis (IPA) on the signature genes of this subcluster gave multiple cancer metastasis associated and EMT signaling pathways, suggesting a critical role of this cluster in leading tumor cell metastasis. Taken together, this study displayed a PDAC cancer subcluster and its marker gene, biologically targeting of which might significantly attenuate the metastasis of tumor and might be a potential strategy for the therapeutic treatment of cancer.

scholarly journals Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2

Oncogene ◽  
2021 ◽  
Vol 40 (17) ◽  
pp. 3164-3179
Author(s):  
Yang Liu ◽  
Tianchi Tang ◽  
Xiaosheng Yang ◽  
Peng Qin ◽  
Pusen Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Noncoding Rna ◽  
Pancreatic Tumor ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Ductal Adenocarcinoma ◽  
Overall Survival Rate ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.

The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

2020 ◽  
pp. 1-23
Author(s):  
Divya Adiga ◽  
Raghu Radhakrishnan ◽  
Sanjiban Chakrabarty ◽  
Prashant Kumar ◽  
Shama Prasada Kabekkodu
Keyword(s):  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cancer Therapeutics ◽  
Growth And Survival ◽  
Mesenchymal Transition ◽  
Microenvironmental Factors ◽  
Favorable Clinical Outcome

Despite substantial advances in the field of cancer therapeutics, metastasis is a significant challenge for a favorable clinical outcome. Epithelial to mesenchymal transition (EMT) is a process of acquiring increased motility, invasiveness, and therapeutic resistance by cancer cells for their sustained growth and survival. A plethora of intrinsic mechanisms and extrinsic microenvironmental factors drive the process of cancer metastasis. Calcium (Ca<sup>2+</sup>) signaling plays a critical role in dictating the adaptive metastatic cell behavior comprising of cell migration, invasion, angiogenesis, and intravasation. By modulating EMT, Ca<sup>2+</sup> signaling can regulate the complexity and dynamics of events leading to metastasis. This review summarizes the role of Ca<sup>2+</sup> signal remodeling in the regulation of EMT and metastasis in cancer.

scholarly journals Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution

2019 ◽  
Author(s):  
Abdel Nasser Hosein ◽  
Huocong Huang ◽  
Zhaoning Wang ◽  
Kamalpreet Parmar ◽  
Wenting Du ◽  
...  
Keyword(s):  
Single Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Genetically Engineered ◽  
Cellular Heterogeneity ◽  
Ductal Adenocarcinoma ◽  
Cell Populations ◽  
Specific Cell ◽  
Cell Heterogeneity ◽  
Mesenchymal Transition

AbstractBackground & AimsPancreatic ductal adenocarcinoma (PDA) is a major cause of cancer-related death with limited therapeutic options available. This highlights the need for improved understanding of the biology of PDA progression. The progression of PDA is a highly complex and dynamic process featuring changes in cancer cells and stromal cells; however, a comprehensive characterization of PDA cancer cell and stromal cell heterogeneity during disease progression is lacking. In this study, we aimed to profile cell populations and understand their phenotypic changes during PDA progression.MethodsWe employed single-cell RNA sequencing technology to agnostically profile cell heterogeneity during different stages of PDA progression in genetically engineered mouse models.ResultsOur data indicate that an epithelial-to-mesenchymal transition of cancer cells accompanies tumor progression. We also found distinct populations of macrophages with increasing inflammatory features during PDA progression. In addition, we noted the existence of three distinct molecular subtypes of fibroblasts in the normal mouse pancreas, which ultimately gave rise to two distinct populations of fibroblasts in advanced PDA, supporting recent reports on intratumoral fibroblast heterogeneity. Our data also suggest that cancer cells and fibroblasts are dynamically regulated by epigenetic mechanisms.ConclusionThis study systematically outlines the landscape of cellular heterogeneity during the progression of PDA. It strongly improves our understanding of the PDA biology and has the potential to aid in the development of therapeutic strategies against specific cell populations of the disease.

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