Xu Yali, Lin Xiaoyan, Xu Jiawen, Jing Haiyan, Qin Yejun, Li Yintao
Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, P.R. China.
Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
J Cancer. 2018 Feb 28;9(6):1078-1087. doi: 10.7150/jca.23596. eCollection 2018.
Sulfotransferase family 1E member 1 (SULT1E1) is known to catalyze sulfoconjugation and play a crucial role in the deactivation of estrogen homeostasis, which is involved in tumorigenesis and the progression of breast and endometrial cancers. Our previous study has shown that the protein levels of SULT1E1 were decreased in breast cancer; however, the underlying mechanism is still poorly understood. In this study, we explored the functional and molecular mechanisms by which SULT1E1 influenced breast cancer. Here, we identified that overexpression of SULT1E1 inhibited breast cancer cell growth through inducing apoptosis and arresting cell cycle progression. Furthermore, enforced expression of SULT1E1 suppressed tumor cell migration and invasion. Moreover, we found that the activation of PPARγ was required for SULT1E1-mediated downregulation of C-myc, Cyclin D1, MMP-2 and MMP-9 as well as for cell apoptosis, migration and invasion. In addition, the overexpression of SULT1E1 significantly inhibited tumor growth . Taken together, our findings indicated that SULT1E1 performed its tumor suppressor characteristics by activating PPARγ, which provided a novel target for patients with breast cancer.
已知磺基转移酶家族1E成员1(SULT1E1)可催化磺基共轭反应,并在雌激素稳态失活中发挥关键作用,而雌激素稳态失调与肿瘤发生以及乳腺癌和子宫内膜癌的进展有关。我们之前的研究表明,乳腺癌中SULT1E1的蛋白水平降低;然而,其潜在机制仍知之甚少。在本研究中,我们探究了SULT1E1影响乳腺癌的功能和分子机制。在此,我们发现SULT1E1的过表达通过诱导细胞凋亡和阻滞细胞周期进程来抑制乳腺癌细胞生长。此外,SULT1E1的强制表达抑制了肿瘤细胞的迁移和侵袭。而且,我们发现SULT1E1介导的C-myc、细胞周期蛋白D1、基质金属蛋白酶-2和基质金属蛋白酶-9的下调以及细胞凋亡、迁移和侵袭需要PPARγ的激活。此外,SULT1E1的过表达显著抑制了肿瘤生长。综上所述,我们的研究结果表明SULT1E1通过激活PPARγ发挥其肿瘤抑制特性,这为乳腺癌患者提供了一个新的靶点。