Epstein Savannah A, Doles Jason D, Dasgupta Aneesha
Department of Anatomy, Cell Biology and Physiology, Indiana School of Medicine, Indianapolis, Indiana, USA.
Curr Opin Support Palliat Care. 2024 Sep 1;18(3):120-125. doi: 10.1097/SPC.0000000000000711. Epub 2024 Jul 15.
Cancer-associated cachexia is a wasting syndrome entailing loss in body mass and a shortened life expectancy. There is currently no effective treatment to abrogate this syndrome, which leads to 20-30% of deaths in patients with cancer. While there have been advancements in defining signaling factors/pathways in cancer-induced muscle wasting, targeting the same in the clinic has not been as successful. Krüppel-like factor 10 (KLF10), a transcription factor implicated in muscle regulation, is regulated by the transforming growth factor-beta signaling pathway. This review proposes KLF10 as a potential convergence point of diverse signaling pathways involved in muscle wasting.
KLF10 was discovered as a target of transforming growth factor-beta decades ago but more recently it has been shown that deletion of KLF10 rescues cancer-induced muscle wasting. Moreover, KLF10 has also been shown to bind key atrophy genes associated with muscle atrophy in vitro .
There is an elevated need to explore targets in cachexia, which will successfully translate into the clinic. Investigating a convergence point downstream of multiple signaling pathways might hold promise in developing effective therapies for cachexia.
癌症相关性恶病质是一种消耗综合征，会导致体重减轻和预期寿命缩短。目前尚无有效的治疗方法来消除这种综合征，它导致20%-30%的癌症患者死亡。虽然在确定癌症诱导的肌肉消耗中的信号因子/信号通路方面取得了进展，但在临床上针对这些靶点的治疗并不成功。Krüppel样因子10（KLF10）是一种参与肌肉调节的转录因子，受转化生长因子-β信号通路调控。本综述提出KLF10可能是参与肌肉消耗的多种信号通路的潜在汇聚点。
几十年前，KLF10被发现是转化生长因子-β的一个靶点，但最近有研究表明，敲除KLF10可挽救癌症诱导的肌肉消耗。此外，体外研究还表明，KLF10能与肌肉萎缩相关的关键萎缩基因结合。
迫切需要探索恶病质的治疗靶点，并成功转化到临床应用中。研究多个信号通路下游的汇聚点可能为开发有效的恶病质治疗方法带来希望。
