COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 12 導致遺傳型乳腺癌的元兇 BRCA1基因具有重要的抑癌作用，能 抑制惡性腫瘤，突變時卻容易提高患乳 腺癌的風險。鄧教授表示，BRCA1也 是導致遺傳型乳腺癌的元兇，並且多數 為三陰性乳腺癌。他們在小鼠模型中證 實，BRCA1在線粒體自噬、線粒體動力 學方面具重要調控作用，可以通過促進 線粒體自噬清除有損傷的線粒體，以及 降低炎症小體活性，抑制手術後乳腺癌 的復發及轉移。 今次研究發現，BRCA1在細胞核和細胞 質中發揮不同作用，能令線粒體維持正 常自我修復的功能（如分裂、融合及自 噬），對細胞健康至關重要。不過，當 BRCA1發生突變或變異時，就會影響乳 腺細胞中線粒體的正常運作。 陳強博士解釋指，這時候乳腺細胞出問 題，是因為裏面線粒體的自噬功能會漸 漸緩慢，令原本需要清除的受損線粒體 大量積累，同時增加了活性氧，激發 炎症小體的活性。他說：「這個過程會 誘發腫瘤相關巨噬細胞的募集，抑制 CD8+T細胞的活性，從而令腫瘤的免 疫微環境發生改變，促進腫瘤發生和 轉移。因此，採用炎症小體抑制劑如 Glibenclamide（格列本脲）等，可以 有效緩解因為BRCA1突變而誘發的乳腺 癌的復發和轉移，這為治療三陰性乳腺 癌開拓了新方向。」 stimulates the body’s own immune system, causing it to release growth-promoting factors that lead to cancer recurrence and metastasis. Therefore, it is imperative to find new effective targets for the treatment of TNBC.’ The Main Cause of Hereditary Breast Cancer The BRCA1 gene plays an important role in suppressing cancer. It can suppress malignant tumours, but when mutated, it can easily increase the risk of breast cancer. Prof Deng explains that BRCA1 is also the main cause of hereditary breast cancer, most of which are TNBC. Prof Deng’s team has also found through experiments on mice that BRCA1 plays an important role in regulating mitochondrial autophagy and mitochondrial dynamics, which can eliminate mitochondrial damage by promoting mitochondrial autophagy and reducing the activity of inflammatory bodies, thereby inhibiting post-surgery recurrence and metastasis of breast cancer. Prof Deng’s latest study has found that BRCA1 plays different roles in the nucleus and cytoplasm, which can help mitochondria maintain normal self-repair functions (such as division, fusion, and autophagy), which are essential for cell health. But when BRCA1 mutates, it will affect the normal function of mitochondria in breast cells. Dr Chen explains that it is when the BRCA1 gene mutates that the problem occurs. The autophagy function of the mitochondria gradually slows down, which causes damaged mitochondria to accumulate instead of being removed. It also increases reactive oxygen species, which stimulates the activity of inflammatory bodies. ‘This process will induce the recruitment of tumour-associated macrophages and inhibit the activity of CD8+ T Cells, thereby changing the immune microenvironment of the tumour and promoting tumorigenesis and metastasis,’ Dr Chen explains. ‘Therefore, the use of inflammatory body inhibitors such as Glibenclamide can effectively relieve the recurrence and metastasis of breast cancer induced by BRCA1 mutation, which opens up a new direction for the treatment of TNBC.’ 研究成果獲國際著名SCI期刊《Advanced Science》作為 封面文章刊登（本期UMagazine的封面也採用了此圖） The study was published as a cover article in the internationally renowned SCI-indexed journal Advanced Science (Image also on the cover of this UMagazine)
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