PDF(Pubmed)
Abstract：
The microtubule-associated protein MAP1B has been implicated in axonal growth and brain development. We found that MAP1B is highly expressed in the most aggressive and deadliest breast cancer subtype, triple-negative breast cancer (TNBC), but not in other subtypes. Expression of MAP1B was found to be highly correlated with poor prognosis. Depletion of MAP1B in TNBC cells impairs cell migration and invasion concomitant with a defect in tumorigenesis. We found that MAP1B interacts with key components for invadopodia formation, cortactin, and Tks5, the latter of which is a PtdIns(3,4)P2-binding and scaffold protein that localizes to invadopodia. We also found that Tks5 associates with microtubules and supports the association between MAP1B and α-tubulin. In accordance with their interaction, depletion of MAP1B leads to Tks5 destabilization, leading to its degradation via the autophagic pathway. Collectively, these findings suggest that MAP1B is a convergence point of the cytoskeleton to promote malignancy in TNBC and thereby a potential diagnostic and therapeutic target for TNBC.
摘要：
微管相关蛋白MAP1B与轴突生长和大脑发育有关。我们发现MAP1B在最具侵袭性和最致命的乳腺癌亚型中高表达，三阴性乳腺癌（TNBC），但不是在其他亚型。发现MAP1B的表达与不良预后高度相关。TNBC细胞中MAP1B的耗尽会损害细胞迁移和侵袭，并伴随着肿瘤发生的缺陷。我们发现MAP1B与关键成分相互作用，皮质肌动蛋白,和Tks5，后者是PtdIns（3,4）P2结合和支架蛋白，定位于invadopodia。我们还发现Tks5与微管相关，并支持MAP1B和α-微管蛋白之间的关联。根据他们的互动,MAP1B的耗尽导致Tks5不稳定，通过自噬途径导致其降解。总的来说，这些发现表明,MAP1B是促进TNBC恶性化的细胞骨架汇合点,因此是TNBC的潜在诊断和治疗靶点.
