PNPLA8是调控三阴性乳腺癌磷脂代谢并促进肿瘤增殖和转移的关键分子（英文）
会议名称：《2024中国肿瘤标志物学术大会暨CACA整合肿瘤学高峰论坛暨第十七届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会》
会议日期：2024年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：PNPLA8 Breast cancer Triple negative Phospholipid Metabolism reprogramming Eicosanoids Migration Invasion Proliferation
摘 要：Background Triple-negative breast cancer(TNBC) is the most aggressive breast cancer subtype and leads to the poorest patient outcomes despite surgery and chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead to the development of novel molecular targets are critically important for improving therapeutic options for treating *** We sought to identify novel therapeutic targets in TNBC by combining genomic and functional studies with lipidomic analysis, which included mechanistic studies to elucidate the pathways that tie lipid profile to critical cancer cell properties. Our studies were performed in a large panel of human breast cancer cell lines and patient *** Comprehensive lipid profiling revealed that phospholipid metabolism is reprogrammed in TNBC cells. We discovered that patatin-like phospholipase domain-containing lipase 8(PNPLA8)is overexpressed in TNBC cell lines and tissues from breast cancer patients. Silencing of PNPLA8disrupted phospholipid metabolic reprogramming in TNBC, particularly affecting the levels of phosphatidylglycerol(PG), phosphatidylcholine(PC), lysophosphatidylcholine(LPC) and glycerophosphocholine(GPC). We showed that PNPLA8 is essential in regulating cell viability,migration and antioxidation in TNBC cells and promoted arachidonic acid and eicosanoid production, which in turn activated PI3K/Akt/Gsk3β and MAPK *** Our study highlights PNPLA8 as key regulator of phospholipid metabolic reprogramming and malignant phenotypes in TNBC, which could be further developed as a novel molecular treatment target.