Asporin promotes pancreatic cancer cell invasion and migration by regulating the epithelial-to-mesenchymal transition (EMT) through both autocrine and paracrine mechanisms

Wang, Lili; Wu, Huanwen; Wang, Li; Zhang, Hui; Lu, Junliang; Liang, Zhiyong; Liu, Tonghua

doi:10.1016/j.canlet.2017.04.001

Cited by 76 publications

(82 citation statements)

References 40 publications

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“…ASPN, a small leucine‐rich proteoglycan expressed highly in activated PSC, activates NF‐ κ B and promotes endothelial mesenchymal transition in pancreatic cancer (Wang et al. ). While its action on pancreatic islets is unknown, Aspn was one of differentially expressed genes in microarray analysis of mouse islets after high fat diet (Imai et al.…”

Section: Discussionmentioning

confidence: 99%

“…While the implication of change in expression of these genes on the property of ECM in pseudoislets remains to be determined, ECM remodeling may aid pseudoislets to maintain insulin secretion over long-term culture. ASPN, a small leucine-rich proteoglycan expressed highly in activated PSC, activates NF-jB and promotes endothelial mesenchymal transition in pancreatic cancer (Wang et al 2017). While its action on pancreatic islets is unknown, Aspn was one of differentially expressed genes in microarray analysis of mouse islets after high fat diet (Imai et al 2008;Roat et al 2014).…”

Section: Discussionmentioning

confidence: 99%

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Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets

et al. 2018

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AbstractsRodent islets are widely used to study the pathophysiology of beta cells and islet function, however, structural and functional differences exist between human and rodent islets, highlighting the need for human islet studies. Human islets are highly variable, deteriorate during culture, and are difficult to genetically modify, making mechanistic studies difficult to conduct and reproduce. To overcome these limitations, we tested whether pseudoislets, created by dissociation and reaggregation of islet cell suspensions, allow for assessment of dynamic islet function after genetic modulation. Characterization of pseudoislets cultured for 1 week revealed better preservation of first‐phase glucose‐stimulated insulin secretion (GSIS) compared with cultured‐intact islets and insulin secretion profiles similar to fresh islets when challenged by glibenclamide and KCl. qPCR indicated that pseudoislets are similar to the original islets for the expression of markers for cell types, beta cell function, and cellular stress with the exception of reduced proinflammatory cytokine genes (IL1B, CCL2, CXCL8). The expression of extracellular matrix markers (ASPN, COL1A1, COL4A1) was also altered in pseudoislets compared with intact islets. Compared with intact islets transduced by adenovirus, pseudoislets transduced by lentivirus showed uniform transduction and better first‐phase GSIS. Lastly, the lentiviral‐mediated delivery of short hairpin RNA targeting glucokinase (GCK) achieved significant reduction of GCK expression in pseudoislets as well as marked reduction of both first and second phase GSIS without affecting the insulin secretion in response to KCl. Thus, pseudoislets are a tool that enables efficient genetic modulation of human islet cells while preserving insulin secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets

et al. 2018

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“…MMPs are the major enzymes that degrade the components of the ECM (24)(25)(26). In the process of developing safe and effective anticancer drugs, analysis of the antimetastatic ability of the drug is particularly important; the inhibition of MMP activity is also regarded as one aim of cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Anticancer effects of isofraxidin against A549 human lung cancer cells via the EGFR signaling pathway

et al. 2018

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Lung cancer is the leading cause of mortality due to tumor malignancy worldwide. In recent years, the treatment of lung cancer with chemotherapy has demonstrated notable resistance and insensitivity. Therefore, it is of great importance to investigate anti‑lung cancer drugs with high efficiency and low toxicity. In the present study, the effects of isofraxidin on lung cancer cells and the associated mechanisms were investigated. The results revealed that, in vivo and in vitro, isofraxidin exhibited marked inhibitory effects on the A549 lung cancer cell line. The results of Cell Counting kit‑8, Transwell migration and Matrigel invasion assays, and flow cytometry to determine apoptosis, revealed that isofraxidin significantly inhibited the proliferation, migration and invasion of A549 cells, and induced the cell apoptosis. Furthermore, western blot analysis demonstrated that isofraxidin treatment led to effects on the expression of apoptosis‑associated proteins, including members of the Bcl‑2 protein family, and invasion‑associated proteins, including matrix metallopeptidase (MMP)‑2 and MMP‑9, which may occur via inhibition of the expression of phosphorylated (p)‑epidermal growth factor receptor, p‑AKT and p‑extracellular signal‑regulated kinase. This regulation of protein expression may contribute to the inhibition of proliferation, migration and invasion of A549lung cancer cells by isofraxidin. In addition, despite the inhibitory effects on the A549 lung cancer cell line, the present study revealed that isofraxidin exhibited low toxicity towards BEAS‑2B normal lung epithelial cells within a certain dose range (0‑160 µM), indicating that isofraxidin may be employed for lung cancer treatment with hypotoxicity and fewer side effects. In conclusion, isofraxidin may be a novel candidate for anti‑lung cancer chemotherapy.

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“…The activation of the EMT process has been proposed as the critical mechanism responsible for the acquisition of drug resistance in pancreatic cancer cells (3,4). Furthermore, EMT has been revealed to contribute to the invasion and metastasis of various types of carcinomas, including pancreatic cancer (5)(6)(7). However, the vital role of EMT in cancer invasion and metastasis has been recently challenged based on murine studies (8,9).…”

Section: Introductionmentioning

confidence: 99%

AREG mediates the epithelial‑mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF‑κB signalling pathway

Wang

Zhang

et al. 2020

Oncol Rep

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Asporin promotes pancreatic cancer cell invasion and migration by regulating the epithelial-to-mesenchymal transition (EMT) through both autocrine and paracrine mechanisms

Cited by 76 publications

References 40 publications

Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets

Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets

Anticancer effects of isofraxidin against A549 human lung cancer cells via the EGFR signaling pathway

AREG mediates the epithelial‑mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF‑κB signalling pathway

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