LIPH promotes metastasis by enriching stem‐like cells in triple‐negative breast cancer
LIPH promotes metastasis by enriching stem‐like cells in triple‐negative breast cancer
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LIPH 通过富集三阴性乳腺癌中的干细胞样细胞来促进转移
DOI：
10.1111/jcmm.15549
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发表时间：
2020-07
影响因子：
5.3
通讯作者：
Caigang Liu
中科院分区：
文献类型：
--
作者：
Yixiao Zhang;Xudong Zhu;Xinbo Qiao;Xi Gu;Jinqi Xue;Yanshuo Han;Lisha Sun;Meizi Cui;Caigang Liu
脂肪酶成员H（LIPH），甘油三酯脂肪酶家族的新成员。其在乳腺癌中表达的临床意义尚不清楚。因此，在这项研究中，我们调查了144名三阴性乳腺癌（TNBC）患者的LIPH与致瘤行为之间的关系。检测了CD 44 +/CD 24 −干细胞样细胞的比例和乳腺球形成能力。还评估了LIPH在乳腺癌细胞迁移和侵袭中的作用。此外，使用Seahorse测定确定LIPH沉默对线粒体呼吸的影响。最后，通过基于串联质量标签的光谱法和蛋白质印迹法确定LIPH沉默对蛋白质表达的影响。我们发现LIPH表达与淋巴结和远处器官转移有关（P = 0.025），导致乳腺癌患者生存率低（P = 0.027）。LIPH敲低显著降低了CD 44 +/CD 24 −干细胞样细胞的比例及其乳腺球形成能力。LIPH沉默促进细胞凋亡，将细胞周期阻滞在G2/M期，减轻线粒体中氧化相关的耗氧速率，并降低代谢。LIPH抑制肿瘤细胞之间的粘附并增强上皮-间质转化。串联质谱分析显示，在LIPH沉默的细胞中有68种蛋白质差异表达，LIPH介导的肿瘤细胞粘附调节依赖于整合素相关的CAPN 2和桩蛋白信号传导。总体而言，我们的研究结果提供了强有力的证据表明LIPH上调促进了TNBC细胞的转移和干性。因此，靶向LIPH是预防TNBC转移的潜在可行策略。
Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple‐negative breast cancer (TNBC) patients. The ratio and mammosphere‐forming ability of CD44+/CD24− stem‐like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag‐based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs (P = 0.025), resulting in poor survival among breast cancer patients (P = 0.027). LIPH knockdown significantly decreased both the ratio of CD44+/CD24− stem‐like cells and their mammosphere‐forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation‐related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial‐mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH‐silenced cells and LIPH‐mediated modulation of tumour cell adhesion depended on integrin‐related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up‐regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.
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DOI：
10.1002/oby.22352
发表时间：
2019-01
期刊：
Obesity (Silver Spring, Md.)
影响因子：
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作者：
Rebello CJ;Greenway FL;Lau FH;Lin Y;Stephens JM;Johnson WD;Coulter AA
通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/s0304-4157(98)00016-1
发表时间：
1998-11-10
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON BIOMEMBRANES
影响因子：
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作者：
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通讯作者：
Verger, R
影响因子：
4.4
作者：
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通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
Rader, DJ