FAM53A Affects Breast Cancer Cell Proliferation, Migration, and Invasion in a p53-Dependent Manner
FAM53A Affects Breast Cancer Cell Proliferation, Migration, and Invasion in a p53-Dependent Manner
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FAM53A 以 p53 依赖性方式影响乳腺癌细胞增殖、迁移和侵袭
DOI：
10.3389/fonc.2019.01244
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发表时间：
2019-11
影响因子：
4.7
通讯作者：
Mi Xiaoyi
中科院分区：
文献类型：
--
作者：
Zhang Jie;Sun Mingfang;Hao Miaomiao;Diao Kexin;Wang Jian;Li Shiping;Cao Qixue;Mi Xiaoyi
FAM 53 A家族是一个未知的蛋白质家族，其在肿瘤发生中的作用尚不清楚。在这项研究中，我们研究了它在乳腺癌中的作用。199例乳腺癌标本的免疫组化染色表明，FAM 53 A水平与p53状态呈负相关。在p53野生型乳腺癌细胞系MCF-7中，FAM 53 A过表达抑制细胞迁移、侵袭和增殖，下调Snail、细胞周期蛋白D1、RhoA、RhoC和MMP 9的表达，并降低丝裂原活化蛋白激酶激酶（MEK）和细胞外信号调节激酶（ERK）的磷酸化。同时，它上调E-cadherin和p21的表达水平。有趣的是，在p53缺失的乳腺癌细胞系MDA-MB-231中观察到相反的趋势。MEK抑制剂PD 98059降低了MCF-7细胞中FAM 53 A敲低和MDA-MB-231细胞中FAM 53 A过表达的生物学效应，表明FAM 53 A通过MEK-ERK途径影响乳腺癌。在MCF-7细胞中沉默TP 53和在MDA-MB-231细胞中稳定表达野生型p53证实了通过MEK/ERK途径的FAM 53 A信号传导的作用取决于细胞的p53状态。这些结果表明，FAM 53 A通过调节MEK-ERK通路在p53阳性乳腺癌中起肿瘤抑制剂的作用，但可能是p53阴性乳腺癌靶向抗癌治疗的潜在候选者。
Family with sequence similarity 53-member A (FAM53A) is an uncharacterized protein with a suspected but unclear role in tumorigenesis. In this study, we examined its role in breast cancer. Immunohistochemical staining of specimens from 199 cases of breast cancer demonstrated that FAM53A levels were negatively correlated with p53 status. In the p53 wild-type breast cancer cell line MCF-7, FAM53A overexpression inhibited cell migration, invasion, and proliferation, downregulated the expression of Snail, cyclin D1, RhoA, RhoC, and MMP9, and decreased mitogen-activated protein kinase kinase (MEK) and extracellular-signal regulated kinase (ERK) phosphorylation. Concurrently, it upregulated E-cadherin and p21 expression levels. Interestingly, opposite trends were observed in the p53-null breast cancer cell line MDA-MB-231. The MEK inhibitor PD98059 reduced the biological effects of FAM53A knockdown in MCF-7 cells and FAM53A overexpression in MDA-MB-231 cells, suggesting that FAM53A affects breast cancer through the MEK-ERK pathway. Silencing TP53 in MCF-7 cells and stably expressing wild-type p53 in MDA-MB-231 cells confirmed that the effects of FAM53A signaling through the MEK/ERK pathway depended on the p53 status of the cells. These results suggest that FAM53A acts as a tumor suppressor in p53-positive breast cancer by modulating the MEK-ERK pathway, but may be a potential candidate for targeted anticancer therapies in p53-negative breast cancer.
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影响因子：
2.9
作者：
Panagopoulos I;Gorunova L;Torkildsen S;Tierens A;Heim S;Micci F
通讯作者：
Micci F
影响因子：
3.7
作者：
Bartel CA;Jackson MW
通讯作者：
Jackson MW
具有序列相似性的家族83，成员B是预后不良的预测指标，也是表达野生型表皮生长因子受体的肺腺癌的潜在治疗靶标。
影响因子：
2.9
作者：
Yamaura T;Ezaki J;Okabe N;Takagi H;Ozaki Y;Inoue T;Watanabe Y;Fukuhara M;Muto S;Matsumura Y;Hasegawa T;Hoshino M;Osugi J;Shio Y;Waguri S;Tamura H;Imai JI;Ito E;Yanagisawa Y;Honma R;Watanabe S;Suzuki H
通讯作者：
Suzuki H
影响因子：
3.7
作者：
Etokebe GE;Zienolddiny S;Kupanovac Z;Enersen M;Balen S;Flego V;Bulat-Kardum L;Radojčić-Badovinac A;Skaug V;Bakke P;Haugen A;Dembic Z
通讯作者：
Dembic Z
影响因子：
6.6
作者：
Suarez-Carmona M;Lesage J;Cataldo D;Gilles C
通讯作者：
Gilles C