Kansakar Urna, Wang Wei, Markovic Vesna, Sossey-Alaoui Khalid
Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Rammelkamp Center for Research, MetroHealth, Cleveland, OH, USA.
Ann Transl Med. 2020 Jul;8(14):900. doi: 10.21037/atm.2020.02.16.
Cancer metastasis is a complex, multistep process that requires tumor cells to evade from the original site and form new tumors at a distant site or a different organ, often via bloodstream or the lymphatic system. Metastasis is responsible for more than 90% of cancer-related deaths. WAVE3 belongs to the Wiskott-Aldrich syndrome protein (WASP) family, which regulate actin cytoskeleton remodeling as well as several aspects of cell migration, invasion, and metastasis. In fact, WAVE3 has been established as a driver of tumor progression and metastasis in cancers from several origins, including triple negative breast cancers (TNBCs), which are classified as the most lethal subtype of breast cancer, due to their resistance to standard of care therapy and highly metastatic behavior. In this review, we will attempt to summarize the recent advances that have been made to understand how WAVE3 contributes to the molecular mechanisms that control cancer progression and metastasis. We will also review the signaling pathways that are involved in the regulation of WAVE3 expression and function to identify potential therapeutic options targeted against WAVE3 for the treatment of patients with metastatic tumors.
癌症转移是一个复杂的多步骤过程,它要求肿瘤细胞逃离原发部位,并常常通过血液循环或淋巴系统在远处部位或不同器官形成新的肿瘤。转移导致了超过90%的癌症相关死亡。WAVE3属于威斯科特-奥尔德里奇综合征蛋白(WASP)家族,该家族调节肌动蛋白细胞骨架重塑以及细胞迁移、侵袭和转移的多个方面。事实上,WAVE3已被确立为多种起源癌症中肿瘤进展和转移的驱动因素,包括三阴性乳腺癌(TNBC),由于其对标准护理疗法的抗性和高度转移行为,TNBC被归类为最致命的乳腺癌亚型。在这篇综述中,我们将试图总结在理解WAVE3如何促成控制癌症进展和转移的分子机制方面所取得的最新进展。我们还将综述参与WAVE3表达和功能调控的信号通路,以确定针对WAVE3的潜在治疗选择,用于治疗转移性肿瘤患者。