TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer.
TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer.
复制标题
TIMELESS 通过 Sp1/ACER2/S1P 轴调节 ER 阳性乳腺癌中的鞘脂代谢和肿瘤细胞生长
DOI：
10.1038/s41419-020-03106-4
复制
发表时间：
2020-10-22
影响因子：
9
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Zhang S;Huang P;Dai H;Li Q;Hu L;Peng J;Jiang S;Xu Y;Wu Z;Nie H;Zhang Z;Yin W;Zhang X;Lu J
乳腺癌是女性最常见的恶性肿瘤之一。生物节律紊乱会大大增加患乳腺癌的风险。本研究旨在探讨昼夜节律基因TIMELESS昼夜节律调节因子（TIM）在雌激素受体（ER）阳性乳腺癌中的生物学功能及其分子机制，为乳腺癌患者提供新的治疗靶点。本研究旨在探讨TIM在乳腺癌组织中的高表达，TIM在乳腺癌组织中的高表达与预后不良有关，尤其是在ER阳性的乳腺癌患者中。此外，我们发现TIM促进细胞增殖和增强线粒体呼吸。TIM与特异性蛋白1（Sp1）相互作用，从而上调碱性神经酰胺酶2（ACER2）的表达。此外，ACER2负责TIM介导的细胞生长和线粒体呼吸的促进作用。总的来说，我们的研究揭示了TIM通过与Sp1相互作用在鞘脂代谢中的新功能。它为乳腺癌的发病机制提供了新的理论解释，靶向TIM可能成为ER阳性乳腺癌的潜在治疗靶点。
Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Here, we explored that the expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with specificity protein 1 (Sp1) which contributes to upregulate the expression of alkaline ceramidase 2 (ACER2). Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Collectively, our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer.
登录
查看更多内容
影响因子：
16.6
作者：
Bianco, Julien N.;Bergoglio, Valerie;Pasero, Philippe
通讯作者：
Pasero, Philippe
影响因子：
4.8
作者：
Mao, Zhehao;Sun, Wei;Mao, Cungui
通讯作者：
Mao, Cungui
影响因子：
13.9
作者：
Mohawk JA;Green CB;Takahashi JS
通讯作者：
Takahashi JS
影响因子：
12.3
作者：
Kaczynski J;Cook T;Urrutia R
通讯作者：
Urrutia R
影响因子：
4.8
作者：
Bielawski, Jacek;Szulc, Zdzislaw M.;Bielawska, Alicja
通讯作者：
Bielawska, Alicja