Should I stay or should I go? Transsulfuration influences invasion and growth in glioblastoma.
Should I stay or should I go? Transsulfuration influences invasion and growth in glioblastoma.
复制标题
DOI：
10.1172/jci176879
复制
发表时间：
2024-02-01
影响因子：
15.9
通讯作者：
Lathia, Justin D.
中科院分区：
文献类型：
--
作者：
Ponti, Andras K.;Silver, Daniel J.;Hine, Christopher;Lathia, Justin D.
治疗胶质母细胞瘤患者的一个主要挑战是无法通过化疗、放疗或手术切除消除高度侵袭性细胞。当癌细胞面临复制或入侵邻近组织的问题时，它们会重新调整代谢，共同努力支持必要的细胞过程，并解释营养丰富度的改变。在本期的JCI中，Garcia等人通过一种综合的基于多组学的方法与CRISPR敲除筛选相结合，将一种创新的基于3D水凝胶的侵入设备与区域患者活检进行了比较。他们的发现阐明了胱硫醚γ-裂解酶（CTH）的作用，CTH是转硫途径中的一种酶，是调节细胞对氧化应激反应的一种手段。CTH介导的胱硫醚半胱氨酸的转换是必要的调节活性氧支持入侵。同时，CTH的抑制抑制侵袭性胶质母细胞瘤表型。然而，抑制CTH导致更大的总体肿瘤质量。这些发现表明，靶向转硫途径可能作为一种手段，重定向胶质母细胞瘤增殖或入侵。
A major challenge in treating patients with glioblastoma is the inability to eliminate highly invasive cells with chemotherapy, radiation, or surgical resection. As cancer cells face the issue of replicating or invading neighboring tissue, they rewire their metabolism in a concerted effort to support necessary cellular processes and account for altered nutrient abundance. In this issue of the JCI, Garcia et al. compared an innovative 3D hydrogel–based invasion device to regional patient biopsies through a comprehensive multiomics-based approach paired with a CRISPR knockout screen. Their findings elucidate a role for cystathionine γ-lyase (CTH), an enzyme in the transsulfuration pathway, as a means of regulating the cellular response to oxidative stress. CTH-mediated conversion of cystathionine to cysteine was necessary for regulating reactive oxygen species to support invasion. Meanwhile, inhibition of CTH suppressed the invasive glioblastoma phenotype. However, inhibiting CTH resulted in a larger overall tumor mass. These findings suggest that targeting the transsulfuration pathway may serve as a means of redirecting glioblastoma to proliferate or invade.