scholarly journals KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway

Author(s):  
Di Che ◽  
Mingshuo Wang ◽  
Juan Sun ◽  
Bo Li ◽  
Tao Xu ◽  
...  

Keratin 6A (KRT6A) belongs to the keratin protein family which is a critical component of cytoskeleton in mammalian cells. Although KRT6A upregulation in non-small cell lung cancer (NSCLC) has been reported, the regulatory mechanism and functional role of KRT6A in NSCLC development have been less well investigated. In this study, KRT6A was confirmed to be highly expressed in NSCLC tissue samples, and its high expression correlated with poor patient prognosis. Furthermore, overexpression of KRT6A promotes NSCLC cell proliferation and invasion. Mechanistically, KRT6A overexpression is sufficient to upregulate glucose-6-phosphate dehydrogenase (G6PD) levels and increase the pentose phosphate pathway flux, an essential metabolic pathway to support cancer cell growth and invasion. In addition, we discovered that lysine-specific demethylase 1A (LSD1) functions upstream to promote KRT6A gene expression. We also found that the MYC family members c-MYC/MYCN are involved in KRT6A-induced G6PD upregulation. Therefore, this study reveals an underappreciated mechanism that KRT6A acts downstream of LSD1 and functions as a pivotal driver for NSCLC progression by upregulating G6PD through the MYC signaling pathway. Together, KRT6A and LSD1 may serve as potential prognostic indictors and therapeutic targets for NSCLC.

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Xiangjie Huang ◽  
Sisi Xiao ◽  
Xinping Zhu ◽  
Yun Yu ◽  
Meng Cao ◽  
...  

Abstract Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes lung cancer cell proliferation and colony formation by directly targeting tumor suppressor, FAS. The expression of FAS was significantly downregulated in NSCLC tissue samples and was negatively correlated with the miR-196b-5p expression. Knocking down FAS activates NFkB signaling and subsequent IL6 secretion, resulting in phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth. Our findings indicated that miR-196b-5p might exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting the miR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.


2017 ◽  
Vol 441 (1-2) ◽  
pp. 1-7 ◽  
Author(s):  
Jia Sun ◽  
Tianxiang Li ◽  
Yinying Zhao ◽  
Lirong Huang ◽  
Hua Sun ◽  
...  

2019 ◽  
Vol 10 (7) ◽  
Author(s):  
Xiao-Na Zhu ◽  
Ping He ◽  
Liang Zhang ◽  
Shuo Yang ◽  
Hui-Lin Zhang ◽  
...  

1997 ◽  
Vol 273 (5) ◽  
pp. L941-L949 ◽  
Author(s):  
Barbara Driscoll ◽  
Lingtao Wu ◽  
Susan Buckley ◽  
Frederick L. Hall ◽  
Kathryn D. Anderson ◽  
...  

To investigate the role of cyclin D1 in the regulation of lung cancer cell growth, we created five stably transfected cell lines carrying a cyclin D1 antisense construct. The transfected cells exhibited a marked decrease in the rate of cell growth, in contrast to the original lines (A549 and NCI-H441). The expression of several cell cycle-regulating proteins, including cyclin A, the cyclin-dependent kinases (cdk) 2 and cdk4, in addition to cyclin D1 itself, was markedly decreased. The expression of one cdk inhibitor, p21WAF1/CIP1, increased in the A549-derived cell lines. A specific target of cyclin D1 activity, the growth-suppressing product of the retinoblastoma gene, pRb, exhibited decreased expression and a decreased level of phosphorylation in the transfected cells. Decreased expression of pRb due to a significant increase in its turnover rate suggested that the stability of the protein may depend on phosphorylation by cyclin D1-dependent cdk activity. In addition to the impact on pRb stability, decreased expression of cyclin D1 induced susceptibility to cell death after withdrawal of exogenous growth factors in the antisense transfected cell lines, a response that was not observed in the original cancer cell lines. We conclude that abrogation of cyclin D1 overexpression in lung cancer cells disrupts several key pathways that are required for uncontrolled cell growth and induces those that lead to cell death after growth factor deprivation. Therefore, we speculate that use of antisense cyclin D1 expression in appropriate gene vectors could be a useful method for retarding lung cancer cell growth in accessible tumors such as those of the lung epithelium.


2013 ◽  
Vol 50 (1) ◽  
pp. 282-288 ◽  
Author(s):  
Srinivas J. Rayaprolu ◽  
Navam S. Hettiarachchy ◽  
Pengyin Chen ◽  
Arvind Kannan ◽  
Andronikos Mauromostakos

2017 ◽  
Vol 37 (3) ◽  
pp. 1793-1803 ◽  
Author(s):  
Xin Liu ◽  
Xin Wu ◽  
Yuefan Ma ◽  
Wenzhang Zhang ◽  
Liang Hu ◽  
...  

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