Abstract A25: Heterozygous deletion of Dicer promotes anoikis and reduces pancreatic cancer metastasis in vivo

2015 ◽  
Author(s):  
Brian Quattrochi ◽  
Brian C. Lewis
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Heterozygous Deletion

scholarly journals Pharmacological Inhibition and Genetic Knockdown of Exchange Protein Directly Activated by cAMP 1 Reduce Pancreatic Cancer Metastasis In Vivo

2014 ◽  
Vol 87 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Muayad Almahariq ◽  
Celia Chao ◽  
Fang C. Mei ◽  
Mark R. Hellmich ◽  
Igor Patrikeev ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Pharmacological Inhibition ◽  
Exchange Protein

scholarly journals A novel in vitro model of metastasis supporting passive shedding hypothesis from murine pancreatic cancer Panc-02

2019 ◽  
Vol 71 (5) ◽  
pp. 989-1002
Author(s):  
M. P. Krzykawski ◽  
R. Krzykawska ◽  
M. Paw ◽  
J. Czyz ◽  
J. Marcinkiewicz
Keyword(s):  
Pancreatic Cancer ◽  
Cell Line ◽  
Cancer Metastasis ◽  
Metastatic Potential ◽  
Blood Stream ◽  
Culture Surface ◽  
Vitro Model ◽  
In Vitro Cell Cultures

Abstract Cancer metastasis is believed to happen through active intravasation but there might be also another way to metastasize. According to passive shedding hypothesis, proposed by Munn et al., tumor cells detach from the tumor mass and passively shed to blood stream through leaky blood vessels. We propose a novel In Vitro Migrational Selection (IVMS) assay that enables the pre-selection of invasive pancreatic cancer Panc-02 cells and create a model of passive shedding. We established invasive sub-cell line of murine pancreatic cancer Panc-02 cells (refered to as Panc02-RS), which exhibited higher metastatic potential in vivo and at the same time decrease in vitro migratory skills, comparing to the initial Panc-02 cell line. In in vitro cell cultures Panc-02 spontaneously detached from the cell culture surface and later reattached and colonized new areas. We believe it can mimic the new way of metastasis, namely passive shedding. We concentrated on Panc-02 model but believe that IVMS might be used to create sub cell lines of many solid tumors to model passive shedding. Our results support the passive shedding hypothesis.

scholarly journals Orai3 Regulates Pancreatic Cancer Metastasis by Encoding a Functional Store Operated Calcium Entry Channel

2021 ◽  
Author(s):  
Samriddhi Arora ◽  
Jyoti Tanwar ◽  
Nutan Sharma ◽  
Suman Saurav ◽  
Rajender K. Motiani
Keyword(s):  
Pancreatic Cancer ◽  
Survival Time ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Mesenchymal Transition

Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate of less than 10%. Most of the PC associated deaths are due to metastasis to secondary sites. Calcium (Ca2+) signaling plays a critical role in regulating hallmarks of cancer progression including cell proliferation, migration and apoptotic resistance. Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous pathway responsible for Ca2+ influx into non-excitable cells. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in 6 PC cell lines and found that Orai3 forms a functional SOCE in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G1 phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first time reports that Orai3 drives aggressive phenotypes of PC cells i.e. migration in vitro and metastasis in vivo. Considering that Orai3 expression is inversely associated with the PC patients survival time, it appears to be a highly attractive therapeutic target.

scholarly journals PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1772
Author(s):  
Taek-In Oh ◽  
Mingyu Lee ◽  
Yoon-Mi Lee ◽  
Geon-Hee Kim ◽  
Daekee Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Lung Cancer ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Metastatic Lung

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial–mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of KrasG12D-driven lung cancer. Mechanistically, PGC1α predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1α and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1α-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer.

scholarly journals Downregulated F-Box/LRR-Repeat Protein 7 Facilitates Pancreatic Cancer Metastasis by Regulating Snail1 for Proteasomal Degradation

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Tang ◽  
Meng Ji ◽  
Xing Liang ◽  
Danlei Chen ◽  
Anan Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Invasion ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Proteasomal Degradation ◽  
Human Pancreatic Cancer ◽  
Mesenchymal Transition ◽  
Repeat Protein ◽  
Panc1 Cell

Pancreatic cancer (PCa) is one of the most aggressive lethal malignancies, and cancer metastasis is the major cause of PCa-associated death. F-box/LRR-repeat protein 7 (FBXL7) regulates cancer metastasis and the chemosensitivity of human pancreatic cancer. However, the clinical significance and biological role of FBXL7 in PCa have been rarely studied. In this study, we found that the expression of FBXL7 was down-regulated in PCa tissues compared with tumor-adjacent tissues, and the low expression of FBXL7 was positively associated with cancer metastasis. Functionally, overexpression of FBXL7 attenuated PANC1 cell invasion, whereas FBXL7 silencing promoted BxPC-3 cell invasion. Forced expression of FBXL7 upregulated the expression of epithelial markers (e.g., E-cadherin) and repressed the expression of mesenchymal markers (e.g., N-cadherin and Vimentin), indicating that FBXL7 negatively regulated the epithelial-mesenchymal transition (EMT) of PCa cells. Furthermore, we identified that FBXL7 repressed the expression of Snail1, a crucial transcription factor of EMT. Mechanistically, FBXL7 bound to Snail1 and promoted its ubiquitination and proteasomal degradation. In vivo studies demonstrated that FBXL7 inhibition promotes PCa metastasis. Taken together, our findings demonstrate that FBXL7 knockdown could efficiently enhance PCa metastasis by regulating Snail1-dependent EMT.

scholarly journals LINC01094 Upregulates LIN28B Expression by Sponging miR-577 to Promote Pancreatic Cancer Proliferation and Metastasis

2021 ◽  
Author(s):  
Chen Luo ◽  
Kang Lin ◽  
Cegui Hu ◽  
Xiaojian Zhu ◽  
Jinfeng Zhu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Rna Binding ◽  
Pancreatic Tumors ◽  
Clinicopathological Parameters ◽  
Cancer Proliferation ◽  
Proliferation And Metastasis ◽  
Non Coding Rnas

Abstract Backgroud: The leading cause of death in pancreatic cancer (PC) patients is the progression of cancer metastasis. Long non-coding RNAs (lncRNAs) play an important role in regulating cancers, however its molecular basis in pancreatic cancer (PC) remains to be explored.Methods: In this study, bioinformatics methods are used to predict the potential pairs of lncRNAs in PC. The clinical significance of LINC01094 are determined by qRT-PCR and explored its correlation with clinicopathological parameters. The biological functions and potential mechanisms of LINC01094 in PC progression are studied in vivo and in vitro. Results: We observe that LINC01094 is markedly overexpressed in pancreatic tumors and is associated with poorer prognosis. Downregulation of LINC01094 decreases PC cell invasion and inhibits tumorigenesis and metastasis in mouse xenografts. LINC01094 acts as a sponge for miR-577, sequestering it and derepressing the expression of its endogenous target the RNA‐binding protein lin‐28 homolog B (LIN28B). Conclusions: Overall, LINC01094 upregulates LIN28B by sponging miR-577, thereby promoting PC proliferation and metastasis. This indicates that LINC01094 can be regarded as a new biomarker or therapeutic target for the treatment of PC.

scholarly journals SIRT1 coordinates with the CRL4B complex to regulate pancreatic cancer stem cells to promote tumorigenesis

2021 ◽  
Author(s):  
Shuai Leng ◽  
Wei Huang ◽  
Yang Chen ◽  
Yang Yang ◽  
Dandan Feng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Metastasis ◽  
Histone Deacetylation ◽  
Sirtuin 1 ◽  
Tumor Xenograft ◽  
Ring E3 Ligase ◽  
Pancreatic Cancer Cells

AbstractPancreatic cancer is a common malignant tumor with poor prognosis. Recently, cancer stem cells (CSCs) were identified in several solid tumors, including pancreatic cancer. Although accumulating evidence indicates that sirtuin 1 (SIRT1) exerts biological functions in various cancers, how it contributes to tumorigenesis and metastasis of pancreatic cancer, as well as its role in CSCs, is still poorly defined. Here we show that SIRT1 interacts with the Cullin 4B (CUL4B)-Ring E3 ligase (CRL4B) complex, which is responsible for H2AK119 monoubiquitination (H2AK119ub1), collaborating as a functional unit. Genome-wide analysis of SIRT1/CUL4B targets identified a cohort of genes, including GRHL3 and FOXO3, critically involved in cell differentiation, growth, and migration. Furthermore, we found that SIRT1 and CUL4B collectively promote the proliferation, autophagy, and invasion of pancreatic cancer cells. Remarkably, we demonstrate that SIRT1/CUL4B promotes CSC-like properties, including increased stemness marker expression and sphere formation. In vivo experiments implied that SIRT1 promoted established tumor xenograft growth, increased tumor-initiating capacity in NOD/SCID mice, and increased CSC frequency. Strikingly, SIRT1 and CUL4B expression is markedly upregulated in a variety of human cancers, including pancreatic cancer. Our data provide a molecular basis for the functional interplay between histone deacetylation and ubiquitination. The results also implicate the SIRT1/CRL4B complex in pancreatic cancer metastasis and stem cell properties, thus supporting SIRT1 as a promising potential target for cancer therapy development.

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