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Abstract：
The p140Cap adaptor protein is a scaffold molecule physiologically expressed in few epithelial tissues, such as the mammary gland, and in differentiated neurons. While the role of p140Cap in mammary gland epithelia is not still understood, we already know that a significant subset of breast cancers express p140Cap. In the subgroup of ERBB2-amplified breast cancers, a high p140Cap status predicts a significantly lower probability of developing a distant event and a clear difference in survival. p140Cap is causal in dampening ERBB2-positive tumor cell progression, impairing tumor onset and growth, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. Since only a few p140Cap interacting proteins have been identified in breast cancer and the molecular complexes and pathways underlying the cancer function of p140Cap are largely unknown, we generated a p140Cap interactome from ERBB2-positive breast cancer cells, identifying cancer specific components and those shared with the synaptic interactome. We identified 373 interacting proteins in cancer cells, including those with functions relevant to cell adhesion, protein homeostasis, regulation of cell cycle and apoptosis, which are frequently deregulated in cancer. Within the interactome, we identified 15 communities (clusters) with topology-functional relationships. In neurons, where p140Cap is key in regulating synaptogenesis, synaptic transmission and synaptic plasticity, it establishes an extensive interactome with proteins that cluster to sub complexes located in the postsynaptic density. p140Cap interactors converge on key synaptic processes, including synaptic transmission, actin cytoskeleton remodeling and cell-cell junction organization. Comparing the breast cancer to the synaptic interactome, we found 39 overlapping proteins, a relatively small overlap. However, cell adhesion and remodeling of actin cytoskeleton clearly emerge as common terms in the shared subset. Thus, the functional signature of the two interactomes is primarily determined by organ/tissue and functional specificity, while the overlap provides a list of shared functional terms, which might be linked to both cancer and neurological functions.
摘要：
p140Cap衔接蛋白是在少数上皮组织中生理表达的支架分子，比如乳腺，分化的神经元。虽然p140Cap在乳腺上皮中的作用尚不清楚，我们已经知道，乳腺癌的一个重要子集表达p140Cap。在ERBB2扩增的乳腺癌亚组中，较高的p140Cap状态预示发生远处事件的概率显著较低,且生存率差异明显.p140Cap是抑制ERBB2阳性肿瘤细胞进展的原因，损害肿瘤的发病和生长，和抵消上皮间质转化，导致转移形成减少。由于在乳腺癌中只鉴定了一些p140Cap相互作用蛋白，p140Cap的癌症功能的分子复合物和通路在很大程度上是未知的，我们从ERBB2阳性乳腺癌细胞中产生了一个p140Cap相互作用组，确定癌症的特定成分和与突触相互作用组共享的成分。我们在癌细胞中鉴定出373种相互作用的蛋白质，包括那些与细胞粘附相关的功能，蛋白质稳态，细胞周期和细胞凋亡的调节，在癌症中经常失调。在互动体内，我们确定了15个具有拓扑-功能关系的社区(集群)。在神经元中，其中p140Cap是调节突触发生的关键，突触传递和突触可塑性，它与蛋白质建立了一个广泛的相互作用组，这些蛋白质聚集成位于突触后密度中的亚复合物。p140Cap相互作用者收敛于关键的突触过程，包括突触传递,肌动蛋白细胞骨架重塑和细胞-细胞连接组织。将乳腺癌与突触相互作用组进行比较，我们发现了39个重叠的蛋白质,相对较小的重叠。然而,肌动蛋白细胞骨架的细胞粘附和重塑显然是共享子集中的常用术语。因此，两个关节间的功能特征主要由器官/组织和功能特异性决定，虽然重叠部分提供了共享功能术语的列表，这可能与癌症和神经功能有关。
