文章：

ASCT2调控脂肪酸代谢诱导基底样乳腺癌的谷氨酰胺成瘾性

ASCT2 Regulates Fatty Acid Metabolism to Trigger Glutamine Addiction in Basal-like Breast Cancer

原文发布日期：30 August 2024

DOI: 10.3390/cancers16173028

类型: Article

开放获取: 是

英文摘要：

As a crucial amino acid, glutamine can provide the nitrogen and carbon sources needed to support cancer cell proliferation, invasion, and metastasis. Interestingly, different types of breast cancer have different dependences on glutamine. This research shows that basal-like breast cancer depends on glutamine, while the other types of breast cancer may be more dependent on glucose. Glutamine transporter ASCT2 is highly expressed in various cancers and significantly promotes the growth of breast cancer. However, the key regulatory mechanism of ASCT2 in promoting basal-like breast cancer progression remains unclear. Our research demonstrates the significant change in fatty acid levels caused by ASCT2, which may be a key factor in glutamine sensitivity. This phenomenon results from the mutual activation between ASCT2-mediated glutamine transport and lipid metabolism via the nuclear receptor PPARα. ASCT2 cooperatively promoted PPARα expression, leading to the upregulation of lipid metabolism. Moreover, we also found that C118P could inhibit lipid metabolism by targeting ASCT2. More importantly, this research identifies a potential avenue of evidence for the prevention and early intervention of basal-like breast cancer by blocking the glutamine–lipid feedback loop.

摘要翻译： 

作为一种关键氨基酸，谷氨酰胺可为癌细胞增殖、侵袭和转移提供必需的氮源和碳源。值得注意的是，不同类型乳腺癌对谷氨酰胺的依赖性存在差异。本研究表明，基底样乳腺癌依赖于谷氨酰胺代谢，而其他类型乳腺癌可能更依赖于葡萄糖代谢。谷氨酰胺转运蛋白ASCT2在多种癌症中高表达，并显著促进乳腺癌生长。然而，ASCT2促进基底样乳腺癌进展的关键调控机制尚不明确。我们的研究揭示了ASCT2引起的脂肪酸水平显著变化，这可能是谷氨酰胺敏感性的关键因素。该现象源于ASCT2介导的谷氨酰胺转运与核受体PPARα调控的脂质代谢之间的相互激活作用。ASCT2协同促进PPARα表达，进而上调脂质代谢水平。此外，我们还发现C118P可通过靶向ASCT2抑制脂质代谢。更重要的是，本研究通过阻断谷氨酰胺-脂质反馈环路，为基底样乳腺癌的预防和早期干预提供了潜在证据路径。

原文链接：

ASCT2 Regulates Fatty Acid Metabolism to Trigger Glutamine Addiction in Basal-like Breast Cancer