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Yếu tố điều tiết chính PNPLA8 thúc đẩy quá trình tái lập trình phospholipid gây ra sự tăng trưởng và di chuyển trong ung thư vú ba âm tính
Tóm tắt
Ung thư vú ba âm tính (TNBC) là loại ung thư vú có tính chất hung dữ nhất và dẫn đến những kết quả kém nhất cho bệnh nhân dù đã được phẫu thuật và điều trị hóa trị. Việc khám phá các cơ chế phân tử mới của TNBC có thể dẫn đến việc phát triển các mục tiêu phân tử mới là vô cùng quan trọng để cải thiện các lựa chọn điều trị cho TNBC. Chúng tôi đã tìm cách xác định các mục tiêu điều trị mới trong TNBC bằng cách kết hợp các nghiên cứu genomics và chức năng với phân tích lipidomic, bao gồm các nghiên cứu cơ chế để làm rõ các con đường liên kết hồ sơ lipid với các tính chất quan trọng của tế bào ung thư. Các nghiên cứu của chúng tôi được thực hiện trên một loạt các dòng tế bào ung thư vú người và mẫu bệnh phẩm của bệnh nhân. Profiling lipid toàn diện đã tiết lộ rằng quá trình chuyển hóa phospholipid đã được lập trình lại trong các tế bào TNBC. Chúng tôi đã phát hiện rằng lipase 8 chứa miền phospholipase giống patatin (PNPLA8) được biểu hiện quá mức trong các dòng tế bào TNBC và mô từ bệnh nhân ung thư vú. Việc làm tắt PNPLA8 đã phá vỡ quá trình chuyển hóa phospholipid trong TNBC, đặc biệt ảnh hưởng đến mức phosphatidylglycerol (PG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) và glycerophosphocholine (GPC). Chúng tôi đã chỉ ra rằng PNPLA8 rất cần thiết trong việc điều chỉnh khả năng sống, di chuyển và chống oxy hóa trong các tế bào TNBC và thúc đẩy sản xuất axit arachidonic và các eicosanoid, từ đó kích hoạt tín hiệu PI3K/Akt/Gsk3β và MAPK. Nghiên cứu của chúng tôi nhấn mạnh PNPLA8 như một yếu tố điều tiết chính trong quá trình tái lập trình chuyển hóa phospholipid và các kiểu hình ác tính trong TNBC, điều này có thể được phát triển thêm như một mục tiêu điều trị phân tử mới.
Từ khóa
#ung thư vú ba âm tính #PNPLA8 #tái lập trình phospholipid #điều trị phân tử #cơ chế phân tửTài liệu tham khảo
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