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.

中文翻译：

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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。


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仍不清楚。因此，在本研究中，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联。测试了 CD44+/CD24- 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 测定确定了 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测定和蛋白质印迹确定了 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相关（ P = 0.025），导致乳腺癌患者生存率较差（ P = 0.027）。 LIPH 敲低显着降低了 CD44 ⁺ /CD24 ^-干细胞样细胞的比率及其乳腺球形成能力。 LIPH 沉默促进细胞凋亡，使细胞周期停滞在 G2/M 期，减轻线粒体中与氧化相关的耗氧率，并减少新陈代谢。 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 68 种蛋白质在 LIPH 沉默的细胞中差异表达，并且 LIPH 介导的肿瘤细胞粘附调节依赖于整合素相关的 CAPN2 和桩蛋白信号传导。总的来说，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，针对 LIPH 是预防 TNBC 转移的潜在可行策略。