Rodrigues-Ferreira Sylvie, Morin Morgane, Guichaoua Gwenn, Moindjie Hadia, Haykal Maria M, Collier Olivier, Stoven Véronique, Nahmias Clara
Gustave Roussy Cancer Center, F-94800 Villejuif, France.
INSERM U981, Université Paris-Saclay, F-94800 Villejuif, France.
Cancers (Basel). 2023 Oct 6;15(19):4870. doi: 10.3390/cancers15194870.
A wide panel of microtubule-associated proteins and kinases is involved in coordinated regulation of the microtubule cytoskeleton and may thus represent valuable molecular markers contributing to major cellular pathways deregulated in cancer. We previously identified a panel of 17 microtubule-related (MT-Rel) genes that are differentially expressed in breast tumors showing resistance to taxane-based chemotherapy. In the present study, we evaluated the expression, prognostic value and functional impact of these genes in breast cancer. We show that 14 MT-Rel genes (, , , , , , , , , , , , , ) are up-regulated in breast tumors compared with adjacent normal tissue. Six of them (, , , , , ) are overexpressed by more than 10-fold in tumor samples and four of them (, , and ) are essential for cell survival. Overexpression of all 14 genes, and underexpression of 3 other MT-Rel genes (, and ) are associated with poor breast cancer patient survival. A Systems Biology approach highlighted three major functional networks connecting the 17 MT-Rel genes and their partners, which are centered on spindle assembly, chromosome segregation and cytokinesis. Our studies identified mitotic Aurora kinases and their substrates as major targets for therapeutic approaches against breast cancer.
多种微管相关蛋白和激酶参与微管细胞骨架的协调调节，因此可能代表有助于癌症中失调的主要细胞途径的有价值分子标志物。我们之前鉴定了一组17个微管相关（MT-Rel）基因，它们在对紫杉烷类化疗耐药的乳腺肿瘤中差异表达。在本研究中，我们评估了这些基因在乳腺癌中的表达、预后价值和功能影响。我们发现，与相邻正常组织相比，14个MT-Rel基因（，，，，，，，，，，，，，）在乳腺肿瘤中上调。其中6个（，，，，，）在肿瘤样本中过表达超过10倍，其中4个（，，和）对细胞存活至关重要。所有14个基因的过表达以及其他3个MT-Rel基因（，和）的低表达与乳腺癌患者的不良生存相关。一种系统生物学方法突出了连接17个MT-Rel基因及其伙伴的三个主要功能网络，这些网络以纺锤体组装、染色体分离和胞质分裂为中心。我们的研究确定有丝分裂极光激酶及其底物是针对乳腺癌治疗方法的主要靶点。
