scholarly journals ERO1L promotes IL6/sIL6R signaling and regulates MUC16 expression to promote CA125 secretion and the metastasis of lung cancer cells

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Yuanyuan lei ◽  
Ruochuan Zang ◽  
Zhiliang Lu ◽  
Guochao Zhang ◽  
Jianbing Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Positive Feedback ◽  
Disulfide Bonds ◽  
Feedback Loop ◽  
Research Subject ◽  
Lung Cancer Cell ◽  
C Terminus ◽  
Feedback Pathway ◽  
Cell Supernatant

Abstract The abnormal secretion of CA125, a classic tumor marker, is usually related to a poor prognosis in various tumors. Thus, this study aimed to explore the potential mechanisms that promote CA125 secretion in lung cancer. By querying the database, the gene endoplasmic reticulum oxidoreductase 1L (ERO1L) was identified and chosen as the research subject. The antibody chips were used to screen the lung cancer cell supernatant and found that the most obvious secreted protein was CA125. ERO1L was found to promote the secretion of IL6R by affecting the formation of disulfide bonds. IL6R bound to IL6 and triggered the activation of the NF-κB signaling pathway. Then, NF-κB bound to the promoter of MUC16, resulting in overexpression of MUC16. The extracellular segment of MUC16 was cleaved to form CA125, while the C terminus of MUC16 promoted the EMT phenotype and the release of IL6, forming a positive feedback pathway. In conclusion, ERO1L might affect the secretion of CA125 through the IL6 signaling pathway and form a positive feedback loop to further promote the development of lung cancer. This might expand the application scope of CA125 in lung cancer.

scholarly journals MALAT1-miR-101-SOX9 feedback loop modulates the chemo-resistance of lung cancer cell to DDP via Wnt signaling pathway

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94317-94329 ◽  
Author(s):  
Wei Chen ◽  
Wei Zhao ◽  
Li Zhang ◽  
Lixin Wang ◽  
Jipeng Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Feedback Loop ◽  
Wnt Signaling Pathway ◽  
Lung Cancer Cell

scholarly journals LGR6 activates the Wnt/β-catenin signaling pathway and forms a β-catenin/TCF7L2/LGR6 feedback loop in LGR6high cervical cancer stem cells

Oncogene ◽  
2021 ◽  
Author(s):  
Qian Feng ◽  
Shan Li ◽  
Hong-Mei Ma ◽  
Wen-Ting Yang ◽  
Peng-Sheng Zheng
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Stem Cell Marker ◽  
Positive Feedback Loop

AbstractThe leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) is considered to be a stem cell marker in many normal tissues and promotes tissue development, regeneration, and repair. LGR6 is also related to the initiation and progression of some malignant tumors. However, the role of LGR6 in cervical cancer has not been reported. Here, immunohistochemistry and western blotting showed that LGR6 was significantly upregulated in cervical cancer, compared with the normal cervix. By analyzing The Cancer Genome Atlas database, LGR6 was found to be correlated with a poor prognosis of cervical cancer. Then, a small population of LGR6high cells isolated by using the fluorescence-activated cell sorting exhibited enhanced properties of cancer stem cells including self-renewal, differentiation, and tumorigenicity. Moreover, RNA sequencing revealed that LGR6 was correlated with the Wnt signaling pathway and TOP/FOP, reverse transcription-PCR, and western blotting further proved that LGR6 could activate the Wnt/β-catenin signaling pathway. Interestingly, LGR6 upregulated the expression of TCF7L2 by activating the Wnt/β-catenin pathway. Then, TCF7L2 combining with β-catenin in the nucleus enhanced LGR6 transcription by binding the promoter of LGR6, which further activated the Wnt signaling to form a positive feedback loop. Thus, our study demonstrated that LGR6 activated a novel β-catenin/TCF7L2/LGR6-positive feedback loop in LGR6high cervical cancer stem cells (CSCs), which provided a new therapeutic strategy for targeting cervical CSCs to improve the prognosis of cervical cancer patients.

scholarly journals Sinomenine inhibits A549 human lung cancer cell invasion by mediating the STAT3 signaling pathway

2016 ◽  
Vol 12 (2) ◽  
pp. 1380-1386 ◽  
Author(s):  
Shulong Jiang ◽  
Yebo Gao ◽  
Wei Hou ◽  
Rui Liu ◽  
Xin Qi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Cancer Cell Invasion ◽  
Lung Cancer Cell ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop

2020 ◽  
Author(s):  
In-Gyu Kim ◽  
Jei-Ha Lee ◽  
Seo-Yeon Kim ◽  
Chang-Kyu Heo ◽  
Rae-Kwon Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Transcriptional Activation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Translocation ◽  
Positive Feedback Loop ◽  
Targeting Therapy ◽  
Mesenchymal Transition

Abstract Cancer stem cells (CSCs) are regarded as essential targets to overcome tumor progression and therapeutic resistance; however, practical targeting approaches are limited. Here, we identify testis-specific Y-like protein 5 (TSPYL5) as a CSC-associated factor that promotes stemness and epithelial-to-mesenchymal transition in therapy-resistant non-small cell lung cancer (NSCLC) cells. Aberrantly activated PI3K/AKT pathway in therapy-resistant NSCLC cells promotes TSPYL5 phosphorylation at threonine-120 (pT120), which inhibits ubiquitination and stabilizes TSPYL5. TSPYL5 pT120 also supports SUMOylation, which leads to its nuclear translocation and functions as a transcriptional repressor of PTEN. Nuclear TSPYL5 also activates the transcription of CSC-associated genes, ALDH1 and CD44. Collectively, TSPYL5 pT120 maintains persistent CSC-like characteristics via transcriptional activation of CSC-associated genes and via a positive-feedback loop between the AKT/TSPYL5/PTEN and PTEN/PI3K/AKT signaling pathways. However, inhibition of TSPYL5 pT120 can block aberrant AKT/TSPYL5/PTEN cyclic signaling and cancer stemness. Our study suggests TSPYL5 as a novel target for cancer therapy.

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