USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity.
USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity.
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USP13通过转换肺俱乐部细胞谱系可塑性驱动肺鳞状细胞癌。
DOI：
10.1186/s12943-023-01892-x
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发表时间：
2023-12-13
期刊：
影响因子：
37.3
通讯作者：
Han, Cecil
中科院分区：
文献类型：
--
作者：
Kwon, Juntae;Zhang, Jinmin;Mok, Boram;Allsup, Samuel;Kim, Chul;Toretsky, Jeffrey;Han, Cecil
肺鳞状细胞癌（LUSC）与高死亡率和有限的靶向治疗相关。USP 13是LUSC中扩增最多的基因之一，但其在肺癌中的作用在很大程度上尚不清楚。在这里，我们通过在KrasG 12 D/+; Trp 53 flox/flox背景（KPU）上过表达USP 13建立了一种新的LUSC小鼠模型。KPU驱动的肺鳞状细胞肿瘤忠实地概括了人类LUSC的关键病理组织学、分子特征和细胞途径。我们发现USP 13改变了气道俱乐部细胞中的谱系决定因子，如NKX 2 -1和SOX 2，并加强了俱乐部细胞对鳞状细胞癌发展的命运。我们发现USP 13和c-MYC之间存在强烈的分子关联，导致小鼠和人肺癌细胞中鳞状细胞程序的上调。总的来说，我们的数据表明，USP 13是俱乐部细胞中谱系可塑性的分子驱动因素，并提供了可能对LUSC治疗具有潜在意义的机制见解。在线版本包含补充材料，可通过10.1186/s12943-023-01892-x获得。
Lung squamous cell carcinoma (LUSC) is associated with high mortality and limited targeted therapies. USP13 is one of the most amplified genes in LUSC, yet its role in lung cancer is largely unknown. Here, we established a novel mouse model of LUSC by overexpressing USP13 on KrasG12D/+; Trp53flox/flox background (KPU). KPU-driven lung squamous tumors faithfully recapitulate key pathohistological, molecular features, and cellular pathways of human LUSC. We found that USP13 altered lineage-determining factors such as NKX2-1 and SOX2 in club cells of the airway and reinforced the fate of club cells to squamous carcinoma development. We showed a strong molecular association between USP13 and c-MYC, leading to the upregulation of squamous programs in murine and human lung cancer cells. Collectively, our data demonstrate that USP13 is a molecular driver of lineage plasticity in club cells and provide mechanistic insight that may have potential implications for the treatment of LUSC. The online version contains supplementary material available at 10.1186/s12943-023-01892-x.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
4.6
作者：
Fukazawa T;Guo M;Ishida N;Yamatsuji T;Takaoka M;Yokota E;Haisa M;Miyake N;Ikeda T;Okui T;Takigawa N;Maeda Y;Naomoto Y
通讯作者：
Naomoto Y
影响因子：
30.8
作者：
Bass, Adam J.;Watanabe, Hideo;Mermel, Craig H.;Yu, Soyoung;Perner, Sven;Verhaak, Roel G.;Kim, So Young;Wardwell, Leslie;Tamayo, Pablo;Gat-Viks, Irit;Ramos, Alex H.;Woo, Michele S.;Weir, Barbara A.;Getz, Gad;Beroukhim, Rameen;O'Kelly, Michael;Dutt, Amit;Rozenblatt-Rosen, Orit;Dziunycz, Piotr;Komisarof, Justin;Chirieac, Lucian R.;LaFargue, Christopher J.;Scheble, Veit;Wilbertz, Theresia;Ma, Changqing;Rao, Shilpa;Nakagawa, Hiroshi;Stairs, Douglas B.;Lin, Lin;Giordano, Thomas J.;Wagner, Patrick;Minna, John D.;Gazdar, Adi F.;Zhu, Chang Qi;Brose, Marcia S.;Cecconello, Ivan;Ribeiro, Ulysses, Jr.;Marie, Suely K.;Dahl, Olav;Shivdasani, Ramesh A.;Tsao, Ming-Sound;Rubin, Mark A.;Wong, Kwok K.;Regev, Aviv;Hahn, William C.;Beer, David G.;Rustgi, Anil K.;Meyerson, Matthew
通讯作者：
Meyerson, Matthew
影响因子：
50.3
作者：
Davis RJ;Welcker M;Clurman BE
通讯作者：
Clurman BE
DOI：
10.1056/nejmoa2105281
发表时间：
2021-06-24
期刊：
The New England journal of medicine
影响因子：
--
作者：
Awad MM;Liu S;Rybkin II;Arbour KC;Dilly J;Zhu VW;Johnson ML;Heist RS;Patil T;Riely GJ;Jacobson JO;Yang X;Persky NS;Root DE;Lowder KE;Feng H;Zhang SS;Haigis KM;Hung YP;Sholl LM;Wolpin BM;Wiese J;Christiansen J;Lee J;Schrock AB;Lim LP;Garg K;Li M;Engstrom LD;Waters L;Lawson JD;Olson P;Lito P;Ou SI;Christensen JG;Jänne PA;Aguirre AJ
通讯作者：
Aguirre AJ