MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors.
MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors.
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DOI：
10.1016/j.ccr.2014.04.027
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发表时间：
2014-07-14
期刊：
影响因子：
50.3
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
Wan L;Lu X;Yuan S;Wei Y;Guo F;Shen M;Yuan M;Chakrabarti R;Hua Y;Smith HA;Blanco MA;Chekmareva M;Wu H;Bronson RT;Haffty BG;Xing Y;Kang Y
Metadherin基因（MTDH）在乳腺癌中被预先扩增并与不良预后相关，但其对肿瘤发生的功能贡献知之甚少。使用代表不同亚型乳腺癌的小鼠模型，我们证明了MTDH通过调节癌基因诱导的扩增和肿瘤起始细胞（TIC）的活性在乳腺肿瘤发生中起着关键作用，而它在很大程度上是正常发育的关键。从机制上讲，MTDH通过与含葡萄球菌核酸酶结构域1（SND 1）相互作用并稳定该结构域，支持乳腺上皮细胞（MEC）在致癌/应激条件下的生存。单独沉默MTDH或SND 1或破坏它们的相互作用会损害TIC在体内的致瘤潜力。最后，MTDH-SND 1相互作用的这种功能意义得到了人乳腺癌样本临床分析的支持。
The Metadherin gene (MTDH) is prevalently amplified in breast cancer and associated with poor prognosis but its functional contribution to tumorigenesis is poorly understood. Using mouse models representing different subtypes of breast cancer, we demonstrated that MTDH plays a critical role in mammary tumorigenesis by regulating oncogene-induced expansion and activities of tumor-initiating cells (TICs), whereas it is largely dispensable for normal development. Mechanistically, MTDH supports the survival of mammary epithelial cells (MECs) under oncogenic/stress conditions by interacting with and stabilizing Staphylococcal nuclease domain-containing 1 (SND1). Silencing MTDH or SND1 individually or disrupting their interaction compromises tumorigenenic potential of TICs in vivo. Finally, this functional significance of MTDH-SND1 interaction is supported by clinical analysis of human breast cancer samples.
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影响因子：
50.3
作者：
Hu G;Chong RA;Yang Q;Wei Y;Blanco MA;Li F;Reiss M;Au JL;Haffty BG;Kang Y
通讯作者：
Kang Y
影响因子：
--
作者：
Emdad, Luni;Das, Swadesh K.;Dasgupta, Santanu;Hu, Bin;Sarkar, Devanand;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
50.3
作者：
Kouros-Mehr, Hosein;Bechis, Seth K.;Werb, Zena
通讯作者：
Werb, Zena
影响因子：
50.3
作者：
Buchwalter G;Hickey MM;Cromer A;Selfors LM;Gunawardane RN;Frishman J;Jeselsohn R;Lim E;Chi D;Fu X;Schiff R;Brown M;Brugge JS
通讯作者：
Brugge JS