极性蛋白 SCRIB 与 SLC3A2 相互作用，调节 ER+乳腺癌的增殖和他莫昔芬耐药性。
Polarity protein SCRIB interacts with SLC3A2 to regulate proliferation and tamoxifen resistance in ER+ breast cancer.
机构信息
Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan.
Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, Japan.
出版信息
Commun Biol. 2022 May 2;5(1):403. doi: 10.1038/s42003-022-03363-3.
Estrogen receptor (ER) positive breast cancer represents 75% of all breast cancers in women. Although patients with ER+ cancers receive endocrine therapies, more than 30% develop resistance and succumb to the disease, highlighting the need to understand endocrine resistance. Here we show an unexpected role for the cell polarity protein SCRIB as a tumor-promoter and a regulator of endocrine resistance in ER-positive breast cancer cells. SCRIB expression is induced by estrogen signaling in a MYC-dependent manner. SCRIB interacts with SLC3A2, a heteromeric component of leucine amino acid transporter SLC7A5. SLC3A2 binds to the N-terminus of SCRIB to facilitate the formation of SCRIB/SLC3A2/LLGL2/SLC7A5 quaternary complex required for membrane localization of the amino acid transporter complex. Both SCRIB and SLC3A2 are required for cell proliferation and tamoxifen resistance in ER+ cells identifying a new role for the SCRIB/SLC3A2 complex in ER+ breast cancer.
雌激素受体（ER）阳性乳腺癌占女性所有乳腺癌的 75%。尽管 ER+癌症患者接受内分泌治疗，但超过 30%的患者会产生耐药性并因此死亡，这凸显了需要了解内分泌耐药性的重要性。在这里，我们发现细胞极性蛋白 SCRIB 具有出乎意料的作用，它是 ER 阳性乳腺癌细胞中的肿瘤促进因子和内分泌抵抗的调节剂。SCRIB 的表达受雌激素信号以 MYC 依赖性的方式诱导。SCRIB 与 SLC3A2 相互作用，SLC3A2 是亮氨酸氨基酸转运蛋白 SLC7A5 的异二聚体组成部分。SLC3A2 与 SCRIB 的 N 端结合，促进氨基酸转运蛋白复合物的膜定位所需的 SCRIB/SLC3A2/LLGL2/SLC7A5 四元复合物的形成。SCRIB 和 SLC3A2 均是 ER+细胞增殖和他莫昔芬耐药所必需的，这确定了 SCRIB/SLC3A2 复合物在 ER+乳腺癌中的新作用。
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