Induced expression of AMOT reverses adriamycin resistance in breast cancer cells

IF 3.3 3区 生物学 Q3 CELL BIOLOGY Cell Biology International Pub Date : 2024-07-17 DOI:10.1002/cbin.12198
Haige Zhang, Yingyi Wang, Ya Gao, Mingming Du, Erhu Pan, Mingliang Sun, Xiaozhi Zhang
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Abstract

Adriamycin (ADR) is widely used against breast cancer, but subsequent resistance always occurs. YAP, a downstream protein of angiomotin (AMOT), importantly contributes to ADR resistance, whereas the mechanism is largely unknown. MCF-7 cells and MDA-MB-231 cells were used to establish ADR-resistant cell. Then, mRNA and protein expressions of AMOT and YAP expressions were determined. After AMOT transfection alone or in combination with YAP, the sensitivity of the cells to ADR were evaluated in vitro by examining cell proliferation, apoptosis, and cell cycle, as well as in vivo by examining tumor growth. Additionally, the expressions of proteins in YAP pathway were determined in AMOT-overexpressing cells. In the ADR-resistant cells, the expression of AMOT was decreased while YAP was increased, respectively, and the nucleus localization of YAP was increased at the same time. After AMOT overexpression, these were inhibited, whereas the cell sensitivity to ADR was enhanced. However, the AMOT-induced changes were significantly suppressed by YAP knockdown. The consistent results in vivo showed that AMOT enhanced the inhibition of ADR on tumor growth, and inhibited YAP signaling, evidenced by decreased levels of YAP, CycD1, and p-ERK. Our data revealed that decreased AMOT contributed to ADR resistance in breast cancer cells, which was importantly negatively mediated YAP. These observations provide a potential therapy against breast cancer with ADR resistance.

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诱导表达 AMOT 可逆转乳腺癌细胞对阿霉素的耐药性。
阿霉素(ADR)被广泛用于治疗乳腺癌,但随后总会出现耐药性。YAP是Angiomotin(AMOT)的下游蛋白,对ADR耐药有重要作用,但其机制尚不清楚。研究人员利用 MCF-7 细胞和 MDA-MB-231 细胞建立了 ADR 抗性细胞。然后测定 AMOT 的 mRNA 和蛋白表达以及 YAP 的表达。在单独转染 AMOT 或与 YAP 联合转染后,通过检测细胞增殖、凋亡和细胞周期评估了体外细胞对 ADR 的敏感性,并通过检测肿瘤生长评估了体内细胞对 ADR 的敏感性。此外,还测定了过表达 AMOT 的细胞中 YAP 通路蛋白的表达情况。在ADR耐药细胞中,AMOT的表达量减少,而YAP的表达量增加,同时YAP的核定位增加。过表达AMOT后,这些现象受到抑制,而细胞对ADR的敏感性却增强了。然而,YAP敲除后,AMOT诱导的变化被明显抑制。体内的一致结果表明,AMOT增强了ADR对肿瘤生长的抑制作用,并抑制了YAP信号转导,表现为YAP、CycD1和p-ERK水平的降低。我们的数据显示,AMOT的减少导致了乳腺癌细胞对ADR的抗性,而这一抗性主要是由YAP负向介导的。这些观察结果为治疗具有 ADR 抗性的乳腺癌提供了一种潜在疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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