Breast cancer is a heterogeneous genetic disease driven by the accumulation of individual mutations per tumor. Whole-genome sequencing approaches have identified numerous genes with recurrent mutations in primary tumors. Although mutations in well characterized tumor suppressors and oncogenes are overrepresented in these sets, the majority of the genetically altered genes have so far unknown roles in breast cancer progression. To improve the basic understanding of the complex disease breast cancer and to potentially identify novel drug targets or regulators of known cancer-driving pathways, we analyzed 86 wild-type genes and 94 mutated variants for their effect on cell growth using a serially constructed panel of MCF7 cell lines. We demonstrate in subsequent experiments that the metal cation transporter CNNM4 regulates growth by induction of apoptosis and identified a tumor suppressive role of complement factor properdin (CFP) in vitro and in vivo. CFP appears to induce the intracellular upregulation of the pro-apoptotic transcription factor DDIT3 which is associated with endoplasmic reticulum-stress response.

中文翻译：

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CFP通过TES介导的转录因子DDIT3上调来抑制乳腺癌细胞的生长。

乳腺癌是一种异质性遗传疾病，由每个肿瘤的单个突变的积累驱动。全基因组测序方法已经鉴定出许多在原发性肿瘤中具有复发突变的基因。尽管特征明确的肿瘤抑制因子和致癌基因中的突变在这些组中被过度表达，但迄今为止大多数遗传改变的基因在乳腺癌进展中的作用尚不清楚。为了提高对复杂疾病乳腺癌的基本了解并潜在地识别已知的癌症驱动途径的新型药物靶标或调节剂，我们使用了一系列的串联结构分析，分析了86种野生型基因和94个突变变体对细胞生长的影响。 MCF7细胞系。我们在随后的实验中证明金属阳离子转运蛋白CNNM4通过诱导细胞凋亡来调节生长，并在体外和体内鉴定了补体因子备解素（CFP）的肿瘤抑制作用。CFP似乎诱导凋亡前转录因子DDIT3的细胞内上调，这与内质网应激反应有关。