scholarly journals Keratin 17 Suppresses Cell Proliferation and Epithelial-Mesenchymal Transition in Pancreatic Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Yong Zeng ◽  
Min Zou ◽  
Yan Liu ◽  
Keting Que ◽  
Yunbing Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Pancreatic Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Cycle Progression ◽  
Mesenchymal Transition

Keratin 17 (K17), a member of type I acidic epithelial keratin family, has been reported to be upregulated in many malignant tumors and to be involved in promoting the development of tumors. However, the precise role of K17 in progression of pancreatic cancer is still unknown. In this study, we found that K17 expression was highly expressed in pancreatic cancer tissues and cell lines and that upregulated expression was associated with the pathological grade and poor prognosis. K17 expression served as an independent predictor of pancreatic cancer survival. Meanwhile, we showed that knocking down K17 induced pancreatic cancer cell proliferation, colony formation and tumor growth in xenografts in mice. However, K17 upregulation inhibited pancreatic cancer cell proliferation and colony formation. Further mechanistic study revealed that K17 knockdown promoted cell cycle progression by upregulating CyclinD1 expression and repressed cell apoptosis. However, K17 upregulation suppressed cell cycle progression by decreasing CyclinD1 expression, and induced apoptosis by increasing the levels of cleaved Caspase3. In addition, K17 knockdown promoted pancreatic cancer cell migration and invasion, but K17 upregulation suppressed cell migration and invasion. Moreover, knocking down K17 promoted epithelial-mesenchymal transition (EMT) in pancreatic cancer cell by inhibiting E-cadherin expression and inducing Vimentin expression, and the effects of K17 upregulation were opposite to that of K17downregulation. Taken together, our findings suggest that K17 functions as a potential tumor suppressor, even though it is upregulated in pancreatic cancer.

scholarly journals Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial–Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1856 ◽  
Author(s):  
Wei ◽  
Penso ◽  
Hackman ◽  
Wang ◽  
Mackenzie
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cancer Cell Growth ◽  
Mesenchymal Transition

Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer cell migration and invasion and the underlying mechanisms. EGCG reduced pancreatic cancer cell growth, migration, and invasion in vitro and in vivo. EGCG prevented “Cadherin switch” and decreased the expression level of TCF8/ZEB1, β-Catenin, and Vimentin. Mechanistically, EGCG inhibited the Akt pathway in a time-dependent manner, by suppressing IGFR phosphorylation and inducing Akt degradation. Co-treatment with catalase or N-Acetyl-L-cysteine did not abrogate EGCG’s effect on the Akt pathway or cell growth. Moreover, EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial–mesenchymal transition markers and inhibiting Akt pathway. In summary, EGCG may prove beneficial to improve gemcitabine sensitivity in inhibiting pancreatic cancer cell migration and invasion, to some extent through the inhibition of Akt pathway and epithelial–mesenchymal transition.

Downregulation of lncRNA AFAP1-AS1 by oridonin inhibits the epithelial-to-mesenchymal transition and proliferation of pancreatic cancer cells

2019 ◽  
Vol 51 (8) ◽  
pp. 814-825 ◽  
Author(s):  
Songmei Lou ◽  
Jian Xu ◽  
Bili Wang ◽  
Shuquan Li ◽  
Jun Ren ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Pancreatic Cancer Cell ◽  
Cycle Progression ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractRecent studies have demonstrated that the expression of the long non-coding RNA (lncRNA) AFAP1-AS1 in pancreatic cancer is negatively correlated with survival and prognosis. However, the effects of oridonin and lncRNA AFAP1-AS1 on the epithelial-to-mesenchymal transition (EMT) and migration of pancreatic cancer cells have not been fully elucidated. Surgery is the only potentially curative method for pancreatic cancer, but postoperative recurrence and metastasis are common. The aim of the present study was to assess the effect of oridonin and lncRNA AFAP1-AS1 silencing on pancreatic cancer cells. The pancreatic cancer cell lines BxPC-3 and PANC-1 cells were transfected with siAFAP1-AS1 and its negative control (siNC). After that, oridonin was used to treat the siAFAP1-AS1-transfected cells. The expression of lncRNA AFAP1-AS1 was downregulated in the pancreatic cancer cell lines BxPC-3 and PANC-1. The apoptosis and cell cycle progression of pancreatic cancer cells were evaluated by flow cytometry and Hoechst 33258 staining. Metastasis and invasion of BxPC-3 and PANC-1 cells were detected by transwell migration assay, real-time cell analysis, and western blot analysis. Cells were transfected with the lentiviral siAFAP1-AS1 and siNC, and tumorigenesis was evaluated in BALB/C nude mice. Immunohistochemical examination was used to verify the effects of oridonin and siAFAP1-AS1 on pancreatic cancer. The results demonstrated that the combination of oridonin and siAFAP1-AS1 inhibited pancreatic cancer cell proliferation, induced apoptosis, arrested cell cycle progression, prevented the migration, regulated EMT-related protein expression in BxPC-3 and PANC-1 cells, and inhibited pancreatic cancer cell tumorigenicity and EMT in nude mice.

The Inhibition of Src Family Kinase Suppresses Pancreatic Cancer Cell Proliferation, Migration, and Invasion

Pancreas ◽  
2014 ◽  
Vol 43 (5) ◽  
pp. 768-776 ◽  
Author(s):  
Dong Wook Je ◽  
Young Moon O ◽  
Young Geon Ji ◽  
Yunkyung Cho ◽  
Dong Hyeon Lee
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Src Family Kinase

scholarly journals MiR-205 Dysregulations in Breast Cancer: The Complexity and Opportunities

2019 ◽  
Vol 5 (4) ◽  
pp. 53 ◽  
Author(s):  
Xiao ◽  
Humphries ◽  
Yang ◽  
Wang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Therapy Resistance ◽  
Cancer Cell Proliferation ◽  
Mesenchymal Transition

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that downregulate target gene expression by imperfect base-pairing with the 3′ untranslated regions (3′UTRs) of target gene mRNAs. MiRNAs play important roles in regulating cancer cell proliferation, stemness maintenance, tumorigenesis, cancer metastasis, and cancer therapeutic resistance. While studies have shown that dysregulation of miRNA-205-5p (miR-205) expression is controversial in different types of human cancers, it is generally observed that miR-205-5p expression level is downregulated in breast cancer and that miR-205-5p exhibits a tumor suppressive function in breast cancer. This review focuses on the role of miR-205-5p dysregulation in different subtypes of breast cancer, with discussions on the effects of miR-205-5p on breast cancer cell proliferation, epithelial–mesenchymal transition (EMT), metastasis, stemness and therapy-resistance, as well as genetic and epigenetic mechanisms that regulate miR-205-5p expression in breast cancer. In addition, the potential diagnostic and therapeutic value of miR-205-5p in breast cancer is also discussed. A comprehensive list of validated miR-205-5p direct targets is presented. It is concluded that miR-205-5p is an important tumor suppressive miRNA capable of inhibiting the growth and metastasis of human breast cancer, especially triple negative breast cancer. MiR-205-5p might be both a potential diagnostic biomarker and a therapeutic target for metastatic breast cancer.

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