a Department of Pediatrics , Pennsylvania State University College of Medicine , Hershey , PA USA.
b WVU Cancer Institute, Department of Biochemistry , West Virginia University , Morgantown , WV USA.
Autophagy. 2018;14(7):1110-1128. doi: 10.1080/15548627.2018.1450020. Epub 2018 Jun 4.
Macroautophagy/autophagy is a fundamental cellular degradation mechanism that maintains cell homeostasis, regulates cell signaling, and promotes cell survival. Its role in promoting tumor cell survival in stress conditions is well characterized, and makes autophagy an attractive target for cancer therapy. Emerging research indicates that autophagy also influences cancer metastasis, which is the primary cause of cancer-associated mortality. However, data demonstrate that the regulatory role of autophagy in metastasis is multifaceted, and includes both metastasis-suppressing and -promoting functions. The metastasis-suppressing functions of autophagy, in particular, have important implications for autophagy-based treatments, as inhibition of autophagy may increase the risk of metastasis. In this review, we discuss the mechanisms and context underlying the role of autophagy in metastasis, which include autophagy-mediated regulation of focal adhesion dynamics, integrin signaling and trafficking, Rho GTPase-mediated cytoskeleton remodeling, anoikis resistance, extracellular matrix remodeling, epithelial-to-mesenchymal transition signaling, and tumor-stromal cell interactions. Through this, we aim to clarify the context-dependent nature of autophagy-mediated metastasis and provide direction for further research investigating the role of autophagy in cancer metastasis.
自噬是一种基本的细胞降解机制，它可以维持细胞内环境的稳定，调节细胞信号通路，并促进细胞存活。它在应激条件下促进肿瘤细胞存活的作用已经得到了很好的描述，这使得自噬成为癌症治疗的一个有吸引力的靶点。新的研究表明，自噬也会影响癌症的转移，而癌症转移是癌症相关死亡的主要原因。然而，数据表明，自噬在转移中的调节作用是多方面的，包括抑制转移和促进转移的功能。自噬的抑制转移功能对基于自噬的治疗具有重要意义，因为抑制自噬可能会增加转移的风险。在这篇综述中，我们讨论了自噬在转移中作用的机制和背景，包括自噬介导的粘着斑动力学调节、整合素信号转导和运输、Rho GTPase 介导的细胞骨架重塑、失巢凋亡抵抗、细胞外基质重塑、上皮间质转化信号以及肿瘤-基质细胞相互作用。通过这些，我们旨在阐明自噬介导的转移的上下文依赖性，并为进一步研究自噬在癌症转移中的作用提供方向。
