铜(Cu),一种必需的微量营养素,在几个生理过程中起着至关重要的作用,包括细胞增殖和血管生成;然而,其失调诱导氧化应激和炎症反应。在几个肿瘤组织中观察到显著的Cu积累。细胞内Cu的生物利用度受到Cu转运蛋白的严格控制,包括铜转运蛋白1(CTR1)和铜转运P型ATP酶α和β(ATP7A和ATP7B),和铜伴侣,包括超氧化物歧化酶1(CCS)和抗氧化剂-1(Atox-1)的铜伴侣。在一些肿瘤组织中,这些诱导细胞内Cu积累的异常与肿瘤进展有关。此外,含Cu分泌酶的功能紊乱,如超氧化物歧化酶3(SOD3),Cu动力学异常的赖氨酰氧化酶(LOX和LOXL1-4)在肿瘤转移中起关键作用。例如,肿瘤组织中SOD3的丢失会诱导氧化应激,促进新生血管形成和上皮-间质转化(EMT)。LOX促进胶原蛋白交联,在转移性生态位形成中起作用。因此,限制性Cu调控可能是抑制肿瘤转移的新策略。然而,目前尚不清楚这些Cu干扰是如何在肿瘤组织中发生的,以及Cu分泌酶的确切分子机制。在这篇评论文章中,我讨论了铜转运蛋白的作用,铜伴侣,和含Cu分泌酶在肿瘤进展中的作用,以更好地了解Cu稳态在肿瘤组织中的作用。
Copper (Cu), an essential micronutrient, plays an essential role in several physiological processes, including cell proliferation and angiogenesis; however, its dysregulation induces oxidative stress and inflammatory responses. Significant Cu accumulation is observed in several tumor tissues. The bioavailability of intracellular Cu is tightly controlled by Cu transporters, including Cu transporter 1 (CTR1) and Cu-transporting P-type ATPase α and β (ATP7A and ATP7B), and Cu chaperones, including Cu chaperone for superoxide dismutase 1 (CCS) and antioxidant-1 (Atox-1). In several tumor tissues, these abnormalities that induce intra-cellular Cu accumulation are involved in tumor progression. In addition, functional disturbance in Cu-containing secretory enzymes, such as superoxide dismutase 3 (SOD3), and lysyl oxidase enzymes (LOX and LOXL1-4) with abnormal Cu dynamics plays a key role in tumor metastasis. For example, the loss of SOD3 in tumor tissues induces oxidative stress, which promotes neovascularization and epithelial-to-mesenchymal transition (EMT). LOX promotes collagen crosslinking, which functions in the metastatic niche formation. Accordingly, restricted Cu regulation may be a novel strategy for the inhibition of tumor metastasis. However, it is unclear how these Cu disturbances occur in tumor tissues and the exact molecular mechanisms underlying Cu secretory enzymes. In this review article, I discuss the role of Cu transporters, Cu chaperones, and Cu-containing secretory enzymes in tumor progression to better understand the role of Cu homeostasis in tumor tissues.