LIPH promotes metastasis by enriching stem‐like cells in triple‐negative breast cancer. Issue 16 (2nd July 2020)

• Record Type: Journal Article
• Authors: Zhang, Yixiao; Zhu, Xudong; Qiao, Xinbo; Gu, Xi; Xue, Jinqi; Han, Yanshuo; Sun, Lisha; Cui, Meizi; Liu, Caigang
• Is Part Of: Journal of cellular and molecular medicine. Volume 24:Issue 16(2020)
• Page Start: 9125
• Page End: 9134
• Publication Date: 2020-07-02
• Subjects: epithelial‐mesenchymal transition -- lipase member H -- metastasis -- prognosis marker -- stem‐like cells -- triple‐negative breast cancer; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.15549
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 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.