Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation.
Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation.
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Nanog 维持 Lkb1 缺陷型肺腺癌的干性并阻止胃分化。
DOI：
10.15252/emmm.202012627
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发表时间：
2021-03-05
影响因子：
11.1
通讯作者：
Ji H
中科院分区：
文献类型：
--
作者：
Tong X;Chen Y;Zhu X;Ye Y;Xue Y;Wang R;Gao Y;Zhang W;Gao W;Xiao L;Chen H;Zhang P;Ji H
Growing evidence supports that LKB1‐deficient KRAS‐driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the KrasLSL‐G12D/+; Lkb1flox/flox (KL) model show strong plasticity, which associates with up‐regulation of stem cell pluripotency genes such as Nanog. Deletion of Nanog in KL model initiates a gastric differentiation program and promotes mucinous lung tumor growth. We find that NANOG is not expressed at a meaningful level in human lung adenocarcinoma (ADC), as well as in human lung invasive mucinous adenocarcinoma (IMA). Gastric differentiation involves activation of Notch signaling, and perturbation of Notch pathway by the γ‐secretase inhibitor LY‐411575 remarkably impairs mucinous tumor formation. In contrast to non‐mucinous tumors, mucinous tumors are resistant to phenformin treatment. Such therapeutic resistance could be overcome through combined treatments with LY‐411575 and phenformin. Overall, we uncover a previously unappreciated plasticity of LKB1‐deficient tumors and identify the Nanog‐Notch axis in regulating gastric differentiation, which holds important therapeutic implication for the treatment of mucinous lung cancer. This study reveals the plasticity of LKB1‐deficient tumors, and identifies the Nanog‐Notch axis in regulating gastric differentiation. Combinational treatment of γ‐secretase inhibitor LY‐411575 and phenformin effectively blocked invasive mucinous adenocarcinoma IMA formation.
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肺浸润性粘液腺癌形态学亚组的临床特征、分子改变和预后比较。
影响因子：
4
作者：
Cai D;Li H;Wang R;Li Y;Pan Y;Hu H;Zhang Y;Gong R;Pan B;Sun Y;Chen H
通讯作者：
Chen H
影响因子：
5.2
作者：
Hyslop, L;Stojkovic, M;Lako, M
通讯作者：
Lako, M
影响因子：
4.1
作者：
Finberg, Karin E.;Sequist, Lecia V.;Iafrate, A. John
通讯作者：
Iafrate, A. John
Nanog通过氧化磷酸化和脂肪酸代谢的肿瘤性变化来代谢重新编程肿瘤发射类样细胞。
影响因子：
29
作者：
Chen CL;Uthaya Kumar DB;Punj V;Xu J;Sher L;Tahara SM;Hess S;Machida K
通讯作者：
Machida K
影响因子：
64.8
作者：
Ji, Hongbin;Ramsey, Matthew R.;Wong, Kwok-Kin
通讯作者：
Wong, Kwok-Kin