Liu Jiayue, Zhao Fangying, Zhang Yan, Lin Zhaoyan, Chen Ji-Long, Diao Hongxiu
Joint Laboratory of Animal Pathogen Prevention and Control of Fujian-Nepal, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Animals (Basel). 2024 Jan 27;14(3):422. doi: 10.3390/ani14030422.
Cancer is the leading cause of death in both humans and companion animals. Canine mammary tumor is an important disease with a high incidence and metastasis rate, and its poor prognosis remains a serious clinical challenge. C6 ceramide is a short-chain sphingolipid metabolite with powerful potential as a tumor suppressor. However, the specific impact of C6 ceramide on canine mammary cancer remains unclear. However, the effects of C6 ceramide in canine mammary cancer are still unclear. Therefore, we investigated the role of C6 ceramide in the progress of canine mammary cancer and explored its potential mechanism. C6 ceramide inhibited cell growth by regulating the cell cycle without involving apoptosis. Additionally, C6 ceramide inhibited the migration and invasion of CHMp cells. In vivo, C6 ceramide decreased tumor growth and metastasis in the lungs without side effects. Further investigation found that the knockdown of EGR3 expression led to a noticeable increase in proliferation and migration by upregulating the expressions of pJAK1 and pSTAT3, thus activating the JAK1/STAT3 signaling pathway. In conclusion, C6 ceramide inhibits canine mammary cancer growth and metastasis by targeting EGR3 through the regulation of the JAK1/STAT3 signaling pathway. This study implicates the mechanisms underlying the anti-tumor activity of C6 ceramide and demonstrates the potential of EGR3 as a novel target for treating canine mammary cancer.
癌症是人类和伴侣动物的主要死因。犬乳腺肿瘤是一种发病率和转移率都很高的重要疾病，其预后不良仍然是一个严峻的临床挑战。C6神经酰胺是一种具有强大抑癌潜力的短链鞘脂代谢物。然而，C6神经酰胺对犬乳腺癌的具体影响仍不清楚。因此，我们研究了C6神经酰胺在犬乳腺癌进展中的作用，并探索了其潜在机制。C6神经酰胺通过调节细胞周期抑制细胞生长，而不涉及细胞凋亡。此外，C6神经酰胺抑制CHMp细胞的迁移和侵袭。在体内，C6神经酰胺可降低肿瘤生长和肺转移，且无副作用。进一步研究发现，敲低EGR3表达会通过上调pJAK1和pSTAT3的表达导致增殖和迁移显著增加，从而激活JAK1/STAT3信号通路。总之，C6神经酰胺通过调节JAK1/STAT3信号通路靶向EGR3来抑制犬乳腺癌的生长和转移。本研究揭示了C6神经酰胺抗肿瘤活性的潜在机制，并证明了EGR3作为治疗犬乳腺癌新靶点的潜力。
