Carboxylesterase 1 regulates peroxisome proliferator-activated receptor gamma to inhibit the growth and metastasis of breast cancer cells

IF 2.9 4区 生物学 Q3 CELL BIOLOGY
Jingli Wen, Lei Geng, Ruohan Wang, Xiaolei Zhang, Yanmin Sui, Xiaofang Liu, Xin Han
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Abstract

Breast cancer is a common malignancy in women, and it has an absence of effective therapies. Carboxylesterase 1 (CES1), a member of the carboxylesterase family, has anti-tumor properties in several types of cancer. However, the function of CES1 in breast cancer remains unclear. Peroxisome proliferator-activated receptor gamma (PPARG) is a downstream regulator of CES1 and exhibits anti-breast cancer properties. Both CES1 and PPARG were downregulated in breast cancer tissues. Low CES1 and PPARG expression were linked to poorer breast cancer survival. We constructed CES1 knockdown and overexpression models of breast cancer cells by CES1 overexpressing plasmids and plasmids containing short hairpin RNA. High expression of CES1 inhibited breast cancer cell proliferation, evidenced by diminished cell viability, decreased DNA replication, and G1 phase arrest. CES1 overexpression decreased the protein levels of CDK2, CDK6 and cyclin B1 in breast cancer cells. CES1 inhibited the Bcl-2/Bax axis and increased Cleaved caspase-3 levels. Transwell assays showed that CES1 inhibited cell migration and invasion. CES1 increased E-cadherin protein expression and decreased Vimentin protein expression. CES1 knockdown facilitated the proliferation, migration, and invasion of breast cancer cells. CES1 was found to regulate PPARG expression in breast cancer cells positively. We transfected PPARG-interfering plasmids into breast cancer cells with CES1 overexpression. Inhibition of PPARG abrogated the anti-growth and anti-metastasis functions of CES1 in breast cancer cells. This study elucidates that CES1 inhibits the malignant progression of breast cancer by up-regulating the expression of PPARG.

Graphical Abstract

羧酸酯酶1调节过氧化物酶体增殖激活受体γ抑制乳腺癌细胞的生长和转移
乳腺癌是女性中一种常见的恶性肿瘤,目前尚无有效的治疗方法。羧酸酯酶1 (CES1)是羧酸酯酶家族的一员,在几种类型的癌症中具有抗肿瘤特性。然而,CES1在乳腺癌中的功能尚不清楚。过氧化物酶体增殖物激活受体γ (PPARG)是CES1的下游调节因子,具有抗乳腺癌特性。CES1和PPARG在乳腺癌组织中均下调。低CES1和PPARG表达与较差的乳腺癌生存有关。我们利用CES1过表达质粒和含有短发夹RNA的质粒构建乳腺癌细胞CES1敲低和过表达模型。高表达CES1抑制乳腺癌细胞增殖,表现为细胞活力降低、DNA复制减少和G1期阻滞。CES1过表达可降低乳腺癌细胞中CDK2、CDK6和细胞周期蛋白B1的蛋白水平。CES1抑制Bcl-2/Bax轴,增加Cleaved caspase-3水平。Transwell实验显示CES1抑制细胞迁移和侵袭。CES1增加E-cadherin蛋白表达,降低Vimentin蛋白表达。CES1敲低促进了乳腺癌细胞的增殖、迁移和侵袭。CES1对乳腺癌细胞中PPARG的表达有正向调节作用。我们将pparg干扰质粒转染到CES1过表达的乳腺癌细胞中。抑制PPARG可消除CES1在乳腺癌细胞中的抗生长和抗转移功能。本研究阐明CES1通过上调PPARG的表达抑制乳腺癌的恶性进展。图形抽象
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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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