PI3K/AKT/mTOR通路
脂肪酸合酶
癌症研究
生物
结直肠癌
雷帕霉素的作用靶点
蛋白激酶B
下调和上调
脂肪生成
蛋白酶体
mTORC1型
信号转导
生物信息学
计算生物学
癌症
酶
细胞生物学
生物化学
基因
遗传学
作者
Abhilash Barpanda,Deeptarup Biswas,Ayushi Verma,Shashwati Parihari,Avinash Singh,Shobhna Kapoor,Chetan Kantharia,Sanjeeva Srivastava
标识
DOI:10.1021/acs.jproteome.2c00646
摘要
Despite recent advancements, the high mortality rate remains a concern in colon cancer (CAC). Identification of therapeutic markers could prove to be a great asset in CAC management. Multiple studies have reported hyperactivation of de novo lipogenesis (DNL), but its association with the pathology is unclear. This study aims to establish the importance as well as the prognostic and therapeutic potential of DNL in CAC. The key lipogenic enzymes fatty acid synthase along with ATP citrate lyase were quantified using an LC–MS/MS-based targeted proteomics approach in the samples along with the matched controls. The potential capacity of the proteins to distinguish between the tumor and controls was demonstrated using random forest-based class prediction analysis using the peptide intensities. Furthermore, in-depth proteomics of DNL inhibition in the CAC cell line revealed the significance of the pathway in proliferation and metastasis. DNL inhibition affected the major signaling pathways, including DNA repair, PI3K–AKT–mTOR pathway, membrane trafficking, proteasome, etc. The study revealed the upregulation of 26S proteasome machinery as a result of the treatment with subsequent induction of apoptosis. Again, in silico molecular docking-based drug repurposing was performed to find potential drug candidates. Furthermore, we have demonstrated that blocking DNL could be explored as a therapeutic option in CAC treatment.
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