Role of Akt in Growth and Survival of PANC-1 Pancreatic Cancer Cells

Even though the tumour suppressive role of PTEN is well-known, its prognostic implications are ambiguous. The objective of this study was to further explore the function of PTEN expression in human pancreatic cancer. The expression of PTEN has been dominant in various human cancers including pancreatic cancer when compared with their matched normal tissues. The pancreatic cancer cells have been divided into PTEN blockade-susceptible and PTEN blockade-impassible groups dependent on targeting PTEN by altering intracellular signaling. The expression of PTEN has led to varying clinical outcomes of pancreatic cancer based on GEO Series (GSE) data analysis and Liptak’s z analysis. Differential dependency to PTEN blockade has been ascertained based on the expression of polo-like kinase1 PLK1 in pancreatic cancer cells. The prognostic value of PTEN also depends on PLK1 expression in pancreatic cancer. Collectively, the present study provides a rationale for targeting PTEN as a promising therapeutic strategy dependent on PLK1 expressions using a companion biomarker discovery platform.

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Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells: role of circ_0000977/miR-153 axis

RNA Biology ◽

10.1080/15476286.2019.1649585 ◽

2019 ◽

Vol 16 (11) ◽

pp. 1592-1603 ◽

Cited By ~ 22

Author(s):

Zheng-Lin Ou ◽

Zhen Luo ◽

Wei Wei ◽

Shuai Liang ◽

Tai-Long Gao ◽

...

Keyword(s):

Pancreatic Cancer ◽

Nk Cells ◽

Cancer Cells ◽

Immune Escape ◽

Pancreatic Cancer Cells

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Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells

Cell Death and Disease ◽

10.1038/cddis.2017.311 ◽

2017 ◽

Vol 8 (7) ◽

pp. e2924-e2924 ◽

Cited By ~ 23

Author(s):

Yuran Gao ◽

Zhicheng Zhang ◽

Kai Li ◽

Liying Gong ◽

Qingzhu Yang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Ectopic Expression ◽

Pancreatic Cancer Cell Line ◽

Mesenchymal Transition ◽

Gemcitabine Resistance ◽

Pancreatic Cancer Cells ◽

Sense Strand ◽

The Impact

AbstractThe acquisition of epithelial–mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance. Knockdown of linc-DYNC2H1-4 decreased the invasive behavior of BxPC-3-Gem cells while ectopic expression of linc-DYNC2H1-4 promoted the acquisition of EMT and stemness of the parental sensitive cells. Linc-DYNC2H1-4 upregulated ZEB1, the EMT key player, which led to upregulation and downregulation of its targets vimentin and E-cadherin respectively, as well as enhanced the expressions of CSC makers Lin28, Nanog, Sox2 and Oct4. Linc-DYNC2H1-4 is mainly located in the cytosol. Mechanically, it could sponge miR-145 that targetsZEB1,Lin28,Nanog,Sox2,Oct4to restore these EMT and CSC-associated genes expressions. We proved thatMMP3, the nearby gene of linc-DYNC2H1-4 in the sense strand, was also a target of miR-145. Downregulation ofMMP3by miR-145 was reverted by linc-DYNC2H1-4, indicating that competing with miR-145 is one of the mechanisms for linc-DYNC2H1-4 to regulateMMP3. In summary, our results explore the important role of linc-DYNC2H1-4 in the acquisition of EMT and CSC, and the impact it has on gemcitabine resistance in pancreatic cancer cells.

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Possible role of autophagy inhibition in hypoxia-induced chemoresistance of pancreatic cancer cells.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.224 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 224-224 ◽

Cited By ~ 4

Author(s):

Yoon Ho Ko ◽

Young-Seok Cho ◽

Hye Sung Won ◽

Eun Kyoung Jeon ◽

Young Seon Hong

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Western Blotting ◽

Pancreatic Cancer Cell Line ◽

Cancer Cell Line ◽

Hypoxic Condition ◽

Human Pancreatic Cancer ◽

Pancreatic Cancer Cells ◽

Autophagy Inhibition

224 Background: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiation therapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. Methods: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions.We evaluated the extent of LC3-II, as an autophagosome marker, induced by gemcitabine, by western blotting to measure the hypoxia- or chemotherapy- induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Next, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed. Results: Compared with normoxia, gemcitabine-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia.However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer.

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