HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway.
HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway.
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DOI：
10.1016/j.stemcr.2017.11.010
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发表时间：
2018-01-09
影响因子：
5.9
通讯作者：
Chang JC
中科院分区：
文献类型：
--
作者：
Liu Y;Choi DS;Sheng J;Ensor JE;Liang DH;Rodriguez-Aguayo C;Polley A;Benz S;Elemento O;Verma A;Cong Y;Wong H;Qian W;Li Z;Granados-Principal S;Lopez-Berestein G;Landis MD;Rosato RR;Dave B;Wong S;Marchetti D;Sood AK;Chang JC
在这里，我们表明，血液和神经表达1-LIKE（HN 1 L）是一种靶向乳腺癌干细胞（BCSC）基因，在25%的全乳腺癌中发生改变，并与三阴性乳腺癌（TNBC）患者的总体或无复发生存期较短显著相关。HN 1 L沉默减少了BCSC的群体，抑制了肿瘤的发生，使化疗耐药肿瘤对多西他赛重新敏感，并阻碍了多种TNBC细胞系来源的异种移植物中的癌症进展。此外，与HN 1 L相关的基因特征与TNBC患者较短的无病生存期相关。我们将HN 1 L定义为参与LEPR-STAT 3信号轴的基因的BCSC转录调节因子，因为HN 1 L结合STAT 3、瘦素受体和MIR-150的推定共有上游序列。我们的数据表明，TNBC中的BCSC依赖于转录调节因子HN 1 L来持续激活LEPR-STAT 3通路，这使其成为预后和BCSC治疗的潜在重要靶点。HN 1 L表达与TNBC患者的较短生存期相关HN 1 L通过促进STAT 3信号通路HN 1 L调节BCSC：LEPR和miR-150的新型转录调节因子，STAT 3的上游调节因子HN 1 L调节的基因签名可以预测TNBC患者的临床结果Yi et al.描述了HN 1 L作为三阴性乳腺癌（TNBC）中乳腺癌干细胞（BCSC）的新型转录调节因子，促进LEPR和miR-150表达并激活STAT 3途径。由于BCSC有助于TNBC的化疗耐药性和转移，因此对HN 1 L的进一步研究将提供新的治疗策略。
Here, we show that HEMATOLOGICAL AND NEUROLOGICAL EXPRESSED 1-LIKE (HN1L) is a targetable breast cancer stem cell (BCSC) gene that is altered in 25% of whole breast cancer and significantly correlated with shorter overall or relapse-free survival in triple-negative breast cancer (TNBC) patients. HN1L silencing reduced the population of BCSCs, inhibited tumor initiation, resensitized chemoresistant tumors to docetaxel, and hindered cancer progression in multiple TNBC cell line-derived xenografts. Additionally, gene signatures associated with HN1L correlated with shorter disease-free survival of TNBC patients. We defined HN1L as a BCSC transcription regulator for genes involved in the LEPR-STAT3 signaling axis as HN1L binds to a putative consensus upstream sequence of STAT3, LEPTIN RECEPTOR, and MIR-150. Our data reveal that BCSCs in TNBC depend on the transcription regulator HN1L for the sustained activation of the LEPR-STAT3 pathway, which makes it a potentially important target for both prognosis and BCSC therapy. HN1L expression is correlated with shorter survival of TNBC patients HN1L regulates BCSCs by promoting the STAT3 signaling pathway HN1L: novel transcription regulator of LEPR and miR-150, upstream regulators of STAT3 HN1L-regulated gene signatures can predict clinical outcomes in TNBC patients Yi et al. describe HN1L as a novel transcription regulator for breast cancer stem cells (BCSCs) in triple-negative breast cancer (TNBC), promoting LEPR and miR-150 expression and activating the STAT3 pathway. Since BCSCs contribute to chemoresistance and metastasis in TNBC, further investigation of HN1L will offer new therapeutic strategies.
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影响因子：
5.2
作者：
Choi, Dong Soon;Blanco, Elvin;Kim, Yoo-Shin;Rodriguez, Angel A.;Zhao, Hong;Huang, Tim Hui-Ming;Chen, Chun-Liang;Jin, Guangxu;Landis, Melissa D.;Burey, Lacey A.;Qian, Wei;Granados, Sergio M.;Dave, Bhuvanesh;Wong, Helen H.;Ferrari, Mauro;Wong, Stephen T. C.;Chang, Jenny C.
通讯作者：
Chang, Jenny C.
影响因子：
3.7
作者：
Kim S;Dubrovska A;Salamone RJ;Walker JR;Grandinetti KB;Bonamy GM;Orth AP;Elliott J;Porta DG;Garcia-Echeverria C;Reddy VA
通讯作者：
Reddy VA
影响因子：
3.7
作者：
Huang S;Chen Y;Wu W;Ouyang N;Chen J;Li H;Liu X;Su F;Lin L;Yao Y
通讯作者：
Yao Y
瘦素信号传导抑制可在雌激素受体阳性或阴性乳腺癌中产生有效的抗肿瘤活性。
影响因子：
7.4
作者：
Gonzalez, Ruben Rene;Watters, Amber;Xu, Yanbo;Singh, Udai P.;Mann, David R.;Rueda, Bo R.;Penichet, Manuel L.
通讯作者：
Penichet, Manuel L.
影响因子：
11.2
作者：
Chang CC;Wu MJ;Yang JY;Camarillo IG;Chang CJ
通讯作者：
Chang CJ