凋亡或程序性细胞死亡在维持稳态方面扮演着至关重要的角色，因此是一个严密调控的过程。凋亡信号的非正常调控可能会促进癌变。被称为凋亡抑制剂5（Api5）的抑制剂在癌症中上调。有趣的是，Api5被证明可以调节细胞凋亡和增殖。为了探究Api5在癌症发生发展中的确切功能意义，我们在此研究Api5在乳腺癌发生发展中的作用。 首先，我们使用TCGA和GENT2数据集进行了基于计算机的分析，以了解乳腺癌患者中API5的表达模式，然后调查印度乳腺癌患者样本中的蛋白质表达情况。为了研究Api5在乳腺癌发生发展中的功能重要性，我们利用MCF10A三维乳腺小叶体系和改变Api5表达的恶性乳腺细胞的球体系来研究由于改变Api5表达而引起的各种表型和分子变化，利用体内肿瘤形成性研究来证实Api5在乳腺癌发生发展中的重要性。基于计算机的分析显示，乳腺癌患者中Api5转录本水平升高，与预后不良相关。在非肿瘤性乳腺小叶体系中过表达Api5导致增加增殖，细胞表现出部分上皮-间充质转化-like 表型，具有更高的迁移潜力和细胞极性的紊乱。此外，在小叶体系发育过程中，Api5的影响通过FGF2激活的PDK1-Akt/cMYC信号和Ras-ERK通路的联合作用来介导。相反，Api5敲低抑制FGF2信号通路会导致减少增殖和乳腺癌细胞在体内肿瘤形成性降低。综上所述，我们的研究确定Api5是调节乳腺癌发生发展中多个事件，包括增殖和通过FGF2信号通路调节凋亡的中心参与者。©2023作者。

Apoptosis or programmed cell death plays a vital role in maintaining homeostasis and, therefore, is a tightly regulated process. Deregulation of apoptosis signalling can favour carcinogenesis. Apoptosis inhibitor 5 (Api5), an inhibitor of apoptosis, is upregulated in cancers. Interestingly, Api5 is shown to regulate both apoptosis and cell proliferation. To address the precise functional significance of Api5 in carcinogenesis here we investigate the role of Api5 in breast carcinogenesis.Initially, we carried out in silico analyses using TCGA and GENT2 datasets to understand expression pattern of API5 in breast cancer patients followed by investigating the protein expression in Indian breast cancer patient samples. To investigate the functional importance of Api5 in breast carcinogenesis, we utilised MCF10A 3D breast acinar cultures and spheroid cultures of malignant breast cells with altered Api5 expression. Various phenotypic and molecular changes induced by altered Api5 expression were studied using these 3D culture models. Furthermore, in vivo tumorigenicity studies were used to confirm the importance of Api5 in breast carcinogenesis.In-silico analysis revealed elevated levels of Api5 transcript in breast cancer patients which correlated with poor prognosis. Overexpression of Api5 in non-tumorigenic breast acinar cultures resulted in increased proliferation and cells exhibited a partial EMT-like phenotype with higher migratory potential and disruption in cell polarity. Furthermore, during acini development, the influence of Api5 is mediated via the combined action of FGF2 activated PDK1-Akt/cMYC signalling and Ras-ERK pathways. Conversely, Api5 knock-down downregulated FGF2 signalling leading to reduced proliferation and diminished in vivo tumorigenic potential of the breast cancer cells.Taken together, our study identifies Api5 as a central player involved in regulating multiple events during breast carcinogenesis including proliferation, and apoptosis through deregulation of FGF2 signalling pathway.© 2023. The Author(s).