Anticipating resistance to KRAS inhibition: a novel role for USP21 in macropinocytosis regulation.
Anticipating resistance to KRAS inhibition: a novel role for USP21 in macropinocytosis regulation.
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DOI：
10.1101/gad.348971.121
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发表时间：
2021-10-01
影响因子：
10.5
通讯作者：
Crawford HC
中科院分区：
文献类型：
--
作者：
Crawford HC
本展望讨论了Hou等人的发现，描述了去遍在蛋白酶USP 21上调巨胞饮营养清除过程的机制，从而拯救PDAC细胞免于Kras灭绝。胰腺导管腺癌（PDAC）是最致命的癌症之一。几乎所有的PDAC都在KRAS基因中含有致癌突变，使其成为治疗的主要靶点。大多数以前直接抑制KRAS的尝试都令人失望，但最近在靶向一些KRAS突变体方面的成功预示着PDAC治疗的新时代。PDAC模型预测，确定KRAS抑制剂耐药机制将是至关重要的。在这一期的《基因与发育》杂志上，侯和他的同事们（pp. 1327-1332）鉴定了一种这样的机制，其中去泛素化酶USP 21上调巨胞饮的营养清除过程，从Kras灭绝中拯救PDAC细胞。
This Outlook discusses the finding by Hou et al. describing the mechanism by which the deubiquitinase USP21 up-regulates the nutrient-scavenging process of macropinocytosis, rescuing PDAC cells from Kras extinction. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Virtually all PDAC harbors an oncogenic mutation in the KRAS gene, making it the prime target for therapy. Most previous attempts to inhibit KRAS directly have been disappointing, but recent success in targeting some KRAS mutants presages a new era in PDAC therapy. Models of PDAC have predicted that identifying KRAS inhibitor resistance mechanisms will be critical. In this issue of Genes & Development, Hou and colleagues (pp. 1327–1332) identify one such mechanism in which the deubiquitinase USP21 up-regulates the nutrient-scavenging process of macropinocytosis, rescuing PDAC cells from Kras extinction.
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