PLOD2 promotes colorectal cancer progression by stabilizing USP15 to activate the AKT/mTOR signaling pathway.
PLOD2 promotes colorectal cancer progression by stabilizing USP15 to activate the AKT/mTOR signaling pathway.
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前胶原赖氨酸，2-氧代戊二酸-5-双加氧酶2(PLOD2)是一种致癌基因，影响多种恶性肿瘤，包括子宫内膜癌、骨肉瘤和胃癌。这些作用主要是由于胶原前体的沉积增加。然而，它的赖氨酰羟基酶功能如何影响结直肠癌等癌症，还需要进行更多的研究。我们目前的结果表明，PLOD2在结直肠癌中的表达升高，其高表达与较差的生存相关。在体外和体内，过表达PLOD2也促进了结直肠癌的增殖、侵袭和转移。此外，PLOD2通过稳定细胞质中的USP15与USP15相互作用，进而激活AKT/mTOR的磷酸化，从而促进结直肠癌的进展。同时，米诺地尔可下调PLOD2的表达，抑制USP15和AKT/mTOR的磷酸化。我们的研究表明，PLOD2在结直肠癌中发挥致癌作用，上调USP15，随后激活AKT/mTOR通路。PLOD2可促进结直肠癌的增殖和转移。PLOD2通过抑制细胞质中泛素化的蛋白质降解与USP15相互作用。USP15随后激活AKT/mTOR信号通路的磷酸化，促进肿瘤的生长和迁移。
Procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase 2 (PLOD2) has been reported as an oncogenic gene, affecting various malignant tumors, including endometrial carcinoma, osteosarcoma, and gastric cancer. These effects are mostly due to the enhanced deposition of collagen precursors. However, more studies need to be conducted on how its lysyl hydroxylase function affects cancers like colorectal carcinoma (CRC). Our present results showed that PLOD2 expression was elevated in CRC, and its higher expression was associated with poorer survival. Overexpression of PLOD2 also facilitated CRC proliferation, invasion, and metastasis in vitro and in vivo. In addition, PLOD2 interacted with USP15 by stabilizing it in the cytoplasm and then activated the phosphorylation of AKT/mTOR, thereby promoting CRC progression. Meanwhile, minoxidil was demonstrated to downregulate the expression of PLOD2 and suppress USP15, and the phosphorylation of AKT/mTOR. Our study reveals that PLOD2 plays an oncogenic role in colorectal carcinoma, upregulating USP15 and subsequently activating the AKT/mTOR pathway. PLOD2 enhances proliferation and metastasis in CRC. PLOD2 interacts with USP15 by inhibiting protein degradation of ubiquitination in the cytoplasm. USP15 subsequently activates the phosphorylation of the AKT/mTOR signaling pathway to promote tumor growth and migration.
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影响因子：
2.9
作者：
Du, Wenwu;Liu, Ning;He, Yi
通讯作者：
He, Yi
影响因子：
5.5
作者：
Qi Y;Xu R
通讯作者：
Xu R
影响因子：
5.2
作者：
Sawicki T;Ruszkowska M;Danielewicz A;Niedźwiedzka E;Arłukowicz T;Przybyłowicz KE
通讯作者：
Przybyłowicz KE
减少肝转移僵硬度可改善转移性结直肠癌对贝伐珠单抗的反应
影响因子：
50.3
作者：
Shen, Ying;Wang, Xiaohong;Schmidt, Thomas
通讯作者：
Schmidt, Thomas
DOI：
10.3791/484
发表时间：
2007-01-01
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Tseng, William;Leong, Xianne;Engleman, Edgar
通讯作者：
Engleman, Edgar