Department of Urology, Centre Hospitalo-Universitaire Pellegrin-Tripode, Victor Segalen School of Medicine, Bordeaux, France.
Urol Oncol. 2010 Sep-Oct;28(5):473-9. doi: 10.1016/j.urolonc.2008.12.018. Epub 2009 Mar 9.
Metastasis remains the main cause of death in both bladder (BCa) and prostate (PCa) cancers. The results of chemotherapy did not show any significant improvement of the survival the past years. Cancer research has led to the identification of signaling pathways involved and molecular targets that could change the natural history. The epithelial-mesenchymal transition (EMT), critical during embryonic development, becomes potentially destructive in many epithelial tumors progression where it is inappropriately activated. The cell-cell and cell-extracellular matrix interactions are altered to release cancer cells, which are able to migrate toward metastatic sites. Hallmarks of EMT include the down-regulation of E-cadherin expression, which is the main component of the adherens junctions. The protein TWIST is a transcriptional repressor of E-cadherin, tumor progression, and metastasis, and could be used as a molecular target to restore the chemosensitivity in BCa and PCa.
We selected the last 5-year basic research literature on EMT and TWIST but also clinical studies on BCa and PCa in which TWIST is overexpressed and could be considered as an efficient prognostic marker and molecular target.
TWIST is considered as a potential oncogene promoting the proliferation and inhibiting the apoptosis. TWIST promotes the synthesis of the pro-angiogenic factor, vascular endothelial growth factor (VEGF) involved in tumor progression and metastasis. Apoptosis and angiogenesis are two essential cancer progression steps in many epithelial tumors, including BCa and PCa.
With the targeted therapy, oncology has entered into a new era, which is going to be critical in cancer treatment in combination with traditional anticancer drugs.
转移仍然是膀胱癌 (BCa) 和前列腺癌 (PCa) 患者死亡的主要原因。近年来,化疗的结果并未显示出生存的显著改善。癌症研究已经确定了涉及的信号通路和分子靶点,这些靶点可能会改变癌症的自然进程。上皮-间充质转化 (EMT) 在胚胎发育过程中至关重要,但在许多上皮肿瘤的进展中,它会被不当激活,从而变得具有潜在破坏性。细胞-细胞和细胞-细胞外基质的相互作用被改变,以释放能够迁移到转移部位的癌细胞。EMT 的标志包括 E-钙粘蛋白表达的下调,E-钙粘蛋白是黏附连接的主要成分。TWIST 蛋白是 E-钙粘蛋白的转录抑制剂,可促进肿瘤进展和转移,可作为恢复 BCa 和 PCa 化疗敏感性的分子靶点。
我们选择了过去 5 年关于 EMT 和 TWIST 的基础研究文献,以及 TWIST 过表达的 BCa 和 PCa 的临床研究,这些研究将 TWIST 视为有效的预后标志物和分子靶点。
TWIST 被认为是一种潜在的致癌基因,可促进增殖并抑制细胞凋亡。TWIST 促进了促血管生成因子血管内皮生长因子 (VEGF) 的合成,VEGF 参与肿瘤的进展和转移。凋亡和血管生成是许多上皮肿瘤(包括 BCa 和 PCa)中两个重要的癌症进展步骤。
随着靶向治疗的出现,肿瘤学已经进入了一个新时代,这将在联合传统抗癌药物治疗癌症方面发挥关键作用。