ROS/KRAS/AMPK Signaling Contributes to Gemcitabine-Induced Stem-like Cell Properties in Pancreatic Cancer

Zhao, Hengqiang; Wu, Shihong; Li, Hehe; Duan, Qing; Zhang, Zhengle; Shen, Qiang; Wang, Chunyou; Yin, Tao

doi:10.1016/j.omto.2019.07.005

Cited by 45 publications

(42 citation statements)

References 53 publications

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“…AMP-activated protein kinase (AMPK) can regulate cellular energy metabolism, and stimulate ATP generation [36]. Activated AMPK promotes glycolysis and enhances cellular differentiation of tumors [37]. These analysis results provide a basis for HP − GC's molecular mechanisms of AS events and provide a basic theory for subsequent experimental verification.…”

Section: Discussionmentioning

confidence: 95%

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Liu

et al. 2020

Cancer Cell Int

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Background: Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP − GC). Methods: The clinical, gene expression profile data and AS events of 138 HP − GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP − GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan-Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP − GC. Finally, splicing networks were constructed using Cytoscape. Results: A total of 48141 AS events and 1041 DEAS events were found in HP − GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. Conclusion: Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP − GC and can be used as prognostic factors to establish an effective nomogram.

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Section: Discussionmentioning

confidence: 95%

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Liu

et al. 2020

Cancer Cell Int

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“… 56 It has been shown that Gemcitabine may induce the stem-like cell properties in pancreatic cancer via the involvement of ROS/KRAS/AMPK signaling pathway. 57 These findings suggest that chemoradiotherapy enhances the stem-like properties of CSCs and the resultant active metastatic colonization.…”

Section: Mechanisms Of Chemoradiotherapy Affecting Tumor Cell Invasiomentioning

confidence: 96%

Adverse effects of chemoradiotherapy on invasion and metastasis of tumor cells

et al. 2020

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The phenomenon of enhanced invasion and metastasis of residual tumor cells has been observed in an increasing number of patients receiving chemoradiotherapy recently, and tumor metastasis will undoubtedly limit patient prognosis. However, the key mechanism by which chemoradiotherapy affects the invasion and metastasis of tumor cells remains unclear. Studies have shown that chemoradiotherapy may directly act on tumor cells and alter the tumor microenvironment, or induce cell apoptosis and autophagy to promote tumor cell survival and metastasis. In this review, we summarize the potential mechanisms by which chemoradiotherapy may affect the biological behavior of tumor cells and open up new avenues for reducing tumor recurrence and metastasis after treatment. These insights will improve the efficacy of chemoradiotherapy.

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“…Zhao et al demonstrated that the mechanism behind GEM's ineffectiveness was that after GEM induces NADPH oxidase activation via nuclear factor κB (NFκB), activated NADPH oxidase upregulates ROS production, which targets the K-Ras/MAPK pathway. In KRAS knockdown experiments, K-Ras was shown to be responsible for the GEM-mediated metabolic reprogramming and stemness of CSCs [123]. The K-Ras/JNK axis was shown to play a central role in maintaining CSCs or cancer stem-like cells (CSLCs) in pancreatic cancer [124].…”

Section: Altered Ras Signaling By Mutant Ras Forms In Cancer Stem Cellsmentioning

confidence: 99%

The effects of mutant Ras proteins on the cell signalome

Takács

Kudlik

Kurilla

et al. 2020

Cancer Metastasis Rev

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The genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/ PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells.

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ROS/KRAS/AMPK Signaling Contributes to Gemcitabine-Induced Stem-like Cell Properties in Pancreatic Cancer

Cited by 45 publications

References 53 publications

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Adverse effects of chemoradiotherapy on invasion and metastasis of tumor cells

The effects of mutant Ras proteins on the cell signalome

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