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G 蛋白偶联受体相关分拣蛋白 1(GASP-1),一种普遍存在的肿瘤标志物,可促进三阴性乳腺癌的增殖和侵袭。

G-protein coupled receptor-associated sorting protein 1 (GASP-1), a ubiquitous tumor marker, promotes proliferation and invasion of triple negative breast cancer.

机构信息

Department of Biology, Temple University College of Science and Technology, PA, USA.

Department of Pathology and Laboratory Medicine, Temple University School of Medicine, PA, USA.

出版信息

Exp Mol Pathol. 2022 Apr;125:104751. doi: 10.1016/j.yexmp.2022.104751. Epub 2022 Feb 2.

Abstract

We have identified the novel protein GASP-1 (G protein coupled receptor-associated sorting protein 1) that appears to be a universal cancer marker and the expression of which in tumor tissue and patient sera is predictive of cancer severity (Tuszynski et al. 2011; Zheng et al. 2012; Zheng 2013; Chang and Tuszynski, 2020). In preliminary results we discovered that a GASP-1 antibody inhibited the growth of the triple negative breast cancer cell line MDA-MB-231 and transient reduction of GASP-1 in these cells decreased their proliferation. To further substantiate these results, we over and under-expressed GASP-1 in stable clones of MDA-MB-231 cells and evaluated their growth and invasive activities. Cells under-expressing GASP-1 failed to grow after 4 days in culture and eventually died. In contrast GASP-1 expressing cells grew exponentially. Similarly, GASP-1 under-expressing cells formed 30% fewer colonies in soft agar as compared to controls and whereas GASP-1 over-expressing cells formed 2-fold more colonies than controls. In tumor cell invasion assays GASP-1 over-expressing cells were over 10-fold more invasive than controls whereas GASP-1 under-expressing cells were over 10-fold less invasive than controls. In IHC staining studies of breast cancer cells, we found that the overexpressed GASP-1 appear in granules of different sizes that are directly correlated with cancer invasiveness. Our results strongly indicate that GASP-1 promotes proliferation and invasion of the triple negative breast cancer cell line MDA-MB-231 and targeting GASP-1 for treatment of breast cancer is indicated.

摘要

我们已经确定了一种新型蛋白 GASP-1(G 蛋白偶联受体相关分拣蛋白 1),它似乎是一种普遍的癌症标志物,其在肿瘤组织和患者血清中的表达可预测癌症的严重程度(Tuszynski 等人,2011 年;Zheng 等人,2012 年;Zheng 2013 年;Chang 和 Tuszynski,2020 年)。在初步研究结果中,我们发现 GASP-1 抗体抑制了三阴性乳腺癌 MDA-MB-231 细胞系的生长,并且这些细胞中 GASP-1 的短暂减少降低了其增殖能力。为了进一步证实这些结果,我们在 MDA-MB-231 细胞的稳定克隆中过表达和低表达 GASP-1,并评估它们的生长和侵袭活性。在培养 4 天后,低表达 GASP-1 的细胞无法生长,最终死亡。相比之下,表达 GASP-1 的细胞呈指数级生长。同样,低表达 GASP-1 的细胞在软琼脂中形成的菌落数量比对照减少 30%,而高表达 GASP-1 的细胞形成的菌落数量比对照增加 2 倍。在肿瘤细胞侵袭实验中,高表达 GASP-1 的细胞比对照细胞的侵袭能力高出 10 倍以上,而低表达 GASP-1 的细胞比对照细胞的侵袭能力低 10 倍以上。在乳腺癌细胞的 IHC 染色研究中,我们发现过度表达的 GASP-1 出现在不同大小的颗粒中,这些颗粒与癌症的侵袭性直接相关。我们的研究结果强烈表明,GASP-1 促进了三阴性乳腺癌细胞系 MDA-MB-231 的增殖和侵袭,针对 GASP-1 进行治疗可能是治疗乳腺癌的一种方法。

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