Carcelen María, Velasquez Carlos, Vidal Verónica, Gutiérrez Olga, Fernández-Luna José L
Instituto de Investigación Vadecilla (IDIVAL), 39011 Santander, Spain.
Servicio de Neurocirugía, Hospital Univesitario Maqués de Valdecilla, 39008 Santander, Spain.
Biomedicines. 2022 May 10;10(5):1104. doi: 10.3390/biomedicines10051104.
Glioblastoma (GBM) is one of the most aggressive cancers, with dismal prognosis despite continuous efforts to improve treatment. Poor prognosis is mostly due to the invasive nature of GBM. Thus, most research has focused on studying the molecular players involved in GBM cell migration and invasion of the surrounding parenchyma, trying to identify effective therapeutic targets against this lethal cancer. Our laboratory discovered the implication of TENM1, also known as ODZ1, in GBM cell migration in vitro and in tumor invasion using different in vivo models. Moreover, we investigated the microenvironmental stimuli that promote the expression of TENM1 in GBM cells and found that macrophage-secreted IL-6 and the extracellular matrix component fibronectin upregulated TENM1 through activation of Stat3. We also described that hypoxia, a common feature of GBM tumors, was able to induce TENM1 by both an epigenetic mechanism and a HIF2α-mediated transcriptional pathway. The fact that TENM1 is a convergence point for various cancer-related signaling pathways might give us a new therapeutic opportunity for GBM treatment. Here, we briefly review the findings described so far about the mechanisms that control the expression of the GBM invasion factor TENM1.
胶质母细胞瘤（GBM）是最具侵袭性的癌症之一，尽管不断努力改进治疗方法，但其预后仍然很差。预后不良主要是由于GBM的侵袭性。因此，大多数研究都集中在研究参与GBM细胞迁移和侵袭周围实质组织的分子机制，试图确定针对这种致命癌症的有效治疗靶点。我们实验室发现了TENM1（也称为ODZ1）在体外GBM细胞迁移以及使用不同体内模型的肿瘤侵袭中的作用。此外，我们研究了促进GBM细胞中TENM1表达的微环境刺激因素，发现巨噬细胞分泌的白细胞介素-6和细胞外基质成分纤连蛋白通过激活Stat3上调TENM1。我们还描述了缺氧（GBM肿瘤的一个常见特征）能够通过表观遗传机制和HIF2α介导的转录途径诱导TENM1。TENM1是各种癌症相关信号通路的汇聚点，这一事实可能为GBM治疗提供新的治疗机会。在这里，我们简要回顾迄今为止关于控制GBM侵袭因子TENM1表达机制的研究发现。
