scholarly journals DLL4 overexpression increases gastric cancer stem/progenitor cell self-renewal ability and correlates with poor clinical outcome via Notch-1 signaling pathway activation

2016 ◽  
Vol 6 (1) ◽  
pp. 245-257 ◽  
Author(s):  
Zhi-Feng Miao ◽  
Hao Xu ◽  
Hui-Mian Xu ◽  
Zhen-Ning Wang ◽  
Ting-Ting Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Outcome ◽  
Signaling Pathway ◽  
Progenitor Cell ◽  
Notch 1 ◽  
Poor Clinical Outcome ◽  
Self Renewal ◽  
Pathway Activation

scholarly journals c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer

1999 ◽  
Vol 14 (5) ◽  
pp. 526 ◽  
Author(s):  
Sehwan Han ◽  
Hong Yong Kim ◽  
Kyeongmee Park ◽  
Hye Jae Cho ◽  
Myung Soo Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Clinical Outcome ◽  
Human Gastric Cancer ◽  
Poor Clinical Outcome

Hedgehog Signaling in Normal and Malignant Hematopoiesis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3381-3381 ◽  
Author(s):  
Akil A. Merchant ◽  
Giselle A. Joseph ◽  
Evan Jones ◽  
Tara Lin ◽  
B. Doug Smith ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Ectopic Expression ◽  
Rt Pcr ◽  
Self Renewal ◽  
Cell Fate Decisions ◽  
Pathway Activation ◽  
Myeloid Leukemias ◽  
Hh Signaling ◽  
Kg1 Cells

Abstract The Hedgehog (Hh) signaling pathway is critical for normal development and dictates the self-renewal, proliferation and differentiation of normal stem cells and progenitors. Aberrant reactivation of Hh signaling has been described in a wide variety of human cancers and its role in normal stem cells suggest that pathway dysregulation contributes to oncogenesis and influences the cell fate decisions in cancer stem cells (CSC). Like their normal counterparts, CSC appear to undergo self-renewal as well as give rise to differentiated progeny, and these properties implicate that CSC are responsible for continual tumor cell production that underlies the initiation, maintenance and progression of clinical disease. Myeloid leukemias have long served as the model system for human CSC, but the cellular processes responsible for regulating these rare biologically distinct cell populations have remained unclear. We hypothesized that Hh pathway activation contributes to the pathogenesis of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and studied Hh signaling in these settings. Using both RT-PCR for pathway components and a Gli1 reporter assay, we have found that Hh signaling is active in several human AML derived cell lines (Kasumi-1, KG1, KG1a) and primary AML and MDS samples. Approximately 80% (19/24) of primary AML samples tested express the downstream effectors GLI1 or GLI2 indicative of active Hh signaling. Furthermore, inhibition of Hh signaling with the naturally derived SMOOTHENED antagonist cyclopamine reduces the clonogenic growth of KG1 cells implicating the pathway in self-renewal. In contrast, cyclopamine failed to affect colony growth in the HL-60 cell line that lacks expression of Hh pathway signaling components, confirming that the effect of Hh inhibition is specific. In addition, the ectopic expression of Gli1 in KG1 cells partially rescued the effect of cyclopamine on colony formation further demonstrating the specific nature of this compound. We also studied normal CD34+ bone marrow cells and found that they expressed components of Hh pathway by RT-PCR. However, in contrast to KG1 cells, cyclopamine had little effect on the recovery of either normal hematopoietic progenitors or stem cells in an in vitro long-term culture assay. Therefore, it appears that Hh inhibition may preferentially inhibit myeloid leukemias. We further studied the role of Hh pathway activation on normal hematopoiesis and developed a transgenic mouse model in which SMOOTHENED is conditionally over-expressed in the myeloid lineage via Cre recombinase activity regulated by the Lysozyme promoter. Analysis of these mice demonstrated only subtle changes in peripheral blood counts, but further analysis of cells expressing the transgene revealed a significant reduction in the number of mature myeloid cells. This was confirmed by analyzing blood cells for the granulocyte marker Gr1 and pan-myeloid marker Mac1, both of which were significantly reduced in the SMOOTHENED over-expressing cells. These defects are reminiscent of MDS and further suggest that the Hh signaling pathway plays a role in normal hematopoiesis. Therefore, aberrant Hh pathway activation is a feature of myeloid leukemias and inhibitors such as cyclopamine may have a therapeutic role in the treatment of AML and MDS.

scholarly journals High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer

2019 ◽  
Vol 10 (14) ◽  
pp. 3172-3178
Author(s):  
Youjin Kim ◽  
Sun-ju Byeon ◽  
Joonyoung Hur ◽  
Kangkook Lee ◽  
Dongin Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Outcome ◽  
Poor Clinical Outcome

Effect of PI3K/Akt Signaling Pathway on PRAS40Thr246 Phosphorylation in Gastric Cancer Cells

2020 ◽  
Author(s):  
Yizhuo LU ◽  
Lianghui LI ◽  
Guoyang WU ◽  
Huiqin ZHUO ◽  
Guoyan LIU ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Cell Group ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Pathway Activation ◽  
Related Proteins ◽  
Proliferation And Invasion

Background: We aimed to investigate the effect of PI3K/Akt signaling pathway on PRAS40Thr246 phosphorylation in gastric cancer cells. Methods: The study was conducted from April 2017 to January 2018 in Zhongshan Hospital, Xiamen University, Xiamen, China. Gastric cancer cells were divided into three groups: gastric cancer cell group, LY294002 group and MK-2206 group. Specific tests were conducted accordingly. Results: Inhibition of PI3K/Akt signaling pathway activation and PRAS40Thr246 phosphorylation could inhibit proliferation and invasion and promote apoptosis of gastric cancer cells, and PRAS40Thr246 phosphorylation could activate PI3K/Akt signaling pathway. Conclusion: The levels of PI3K/Akt signaling pathway related proteins and p-PRAS40Thr246 were significantly increased in gastric cancer cells. p-PRAS40-Thr246 was able to reflect the activation of the PI3K/Akt signaling pathway, reflecting the sensitivity of the PI3K/AKT signaling pathway to inhibitors.

Overexpression of GOLPH3 is associated with poor clinical outcome in gastric cancer

Tumor Biology ◽  
2012 ◽  
Vol 34 (1) ◽  
pp. 515-520 ◽  
Author(s):  
Ben-Shun Hu ◽  
Hao Hu ◽  
Cong-Yuan Zhu ◽  
Yuan-Long Gu ◽  
Jian-Ping Li
Keyword(s):  
Gastric Cancer ◽  
Clinical Outcome ◽  
Poor Clinical Outcome
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