NLRX1 functions as a tumor suppressor in Pan02 pancreatic cancer cells.
NLRX1 functions as a tumor suppressor in Pan02 pancreatic cancer cells.
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DOI：
10.3389/fonc.2023.1155831
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
胰腺癌是一种致命的恶性肿瘤，治疗选择有限。NLRX 1是Nod样受体（NLR）模式识别受体家族中一个独特的、研究不足的成员，它调节与胰腺癌高度相关的各种生物学过程。NLRX 1在癌症中的作用仍然非常神秘，一些研究将其定义为肿瘤促进剂，而另一些研究则将其描述为肿瘤抑制。这些看似矛盾的作用似乎是由于，至少部分是由于细胞类型和时间机制。在这里，我们定义了NLRX 1在调节胰腺癌的关键标志中的作用，在小鼠Pan 02细胞中使用功能获得和功能丧失研究。我们的数据表明，NLRX 1增加了细胞死亡的易感性，同时也抑制了增殖，迁移和活性氧的产生。我们还表明，NLRX 1可以防止Pan 02细胞中线粒体活性上调，并限制能量产生。转录组学分析显示，与NLRX 1相关的保护性表型与NF-κB、MAPK、AKT和炎性体信号转导的减弱相关。总之，这些数据表明，NLRX 1减少了胰腺癌细胞中与癌症相关的生物学功能，并确立了这种独特的NLR在肿瘤抑制中的作用。
Pancreatic cancer is a deadly malignancy with limited treatment options. NLRX1 is a unique, understudied member of the Nod-like Receptor (NLR) family of pattern recognition receptors that regulates a variety of biological processes that are highly relevant to pancreatic cancer. The role of NLRX1 in cancer remains highly enigmatic, with some studies defining its roles as a tumor promoter, while others characterize its contributions to tumor suppression. These seemingly contradicting roles appear to be due, at least in part, to cell type and temporal mechanisms. Here, we define roles for NLRX1 in regulating critical hallmarks of pancreatic cancer using both gain-of-function and loss-of-function studies in murine Pan02 cells. Our data reveals that NLRX1 increases susceptibility to cell death, while also suppressing proliferation, migration, and reactive oxygen species production. We also show that NLRX1 protects against upregulated mitochondrial activity and limits energy production in the Pan02 cells. Transcriptomics analysis revealed that the protective phenotypes associated with NLRX1 are correlated with attenuation of NF-κB, MAPK, AKT, and inflammasome signaling. Together, these data demonstrate that NLRX1 diminishes cancer-associated biological functions in pancreatic cancer cells and establishes a role for this unique NLR in tumor suppression.
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影响因子：
12.8
作者：
Hong IS
通讯作者：
Hong IS
DOI：
10.1084/jem.20161707
发表时间：
2017-06-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Daley D;Mani VR;Mohan N;Akkad N;Pandian GSDB;Savadkar S;Lee KB;Torres-Hernandez A;Aykut B;Diskin B;Wang W;Farooq MS;Mahmud AI;Werba G;Morales EJ;Lall S;Wadowski BJ;Rubin AG;Berman ME;Narayanan R;Hundeyin M;Miller G
通讯作者：
Miller G
影响因子：
12.4
作者：
Correia, J. da Silva;Miranda, Y.;Ulevitch, R. J.
通讯作者：
Ulevitch, R. J.
影响因子：
8.8
作者：
Koblansky AA;Truax AD;Liu R;Montgomery SA;Ding S;Wilson JE;Brickey WJ;Mühlbauer M;McFadden RM;Hu P;Li Z;Jobin C;Lund PK;Ting JP
通讯作者：
Ting JP
影响因子：
2.7
作者：
Fan, Zhe;Pan, Jiyong;Zhang, Yewei
通讯作者：
Zhang, Yewei