Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Hubei Hongshan Laboratory, Wuhan 430070, China.
Int J Mol Sci. 2022 Aug 5;23(15):8730. doi: 10.3390/ijms23158730.
The breakdown of lipid droplets (LDs) provides energy and contributes to the proliferation and migration of cancer cells. Recent studies have suggested that motility plays a key role in LD breakdown. However, the molecular mechanisms underlying LD motility were poorly characterized. In this study, we examined the function of microfilament-associated proteins 2 and 3 (ARP2 and ARP3) in regulating LDs’ motility in Hela cells. ARP2/3 mediated the LDs’ physical contact with F-actin and promoted the recruitment of Myosin Heavy Chain 9 (MYH9). MYH9 regulated the LD content by binding with LDs and ARP2/3. The number of LDs and TG content was increased after MYH9 interfered. The genes related to FA-related genes and neutral lipid synthesis-related genes were significantly increased (p < 0.05) when ARP2 and ARP3 were overexpressed. Bioinformatic analysis indicated that the high expression of ARP2/3 was associated with a poorer prognosis in cervical squamous cell carcinoma (CSCC). This study showed the effect of cytoskeletal filaments on LD metabolism in cancer cells.
脂滴（LDs）的分解提供能量，并有助于癌细胞的增殖和迁移。最近的研究表明，运动在 LD 分解中起着关键作用。然而，LD 运动的分子机制尚未得到很好的描述。在这项研究中，我们研究了微丝相关蛋白 2 和 3（ARP2 和 ARP3）在调节 Hela 细胞中 LD 运动中的功能。ARP2/3 介导 LD 与 F-肌动蛋白的物理接触，并促进肌球蛋白重链 9（MYH9）的募集。MYH9 通过与 LD 和 ARP2/3 结合来调节 LD 含量。在 MYH9 干扰后，LD 的数量和 TG 含量增加。当 ARP2 和 ARP3 过表达时，与 FA 相关基因和中性脂质合成相关基因显著增加（p<0.05）。生物信息学分析表明，ARP2/3 的高表达与宫颈鳞状细胞癌（CSCC）的预后较差相关。这项研究表明细胞骨架丝对癌细胞中 LD 代谢的影响。
