Department of Orthopaedics, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Int J Mol Sci. 2020 Jul 2;21(13):4720. doi: 10.3390/ijms21134720.
Mechanical regulation is known as an important regulator in cancer progression and malignancy. High shear force has been found to inhibit the cell cycle progression and result in cell death in various cancer cells. Stearoyl-CoA desaturase (SCD)-1, one of the important lipogenic enzymes, has recently been indicated as a potential pharmaceutical target in cancer therapy. In this study, we determined whether the cell fate control of shear force stimulation is through regulating the SCD-1 expression in cancer cells. Human MG63 osteosarcoma cells were used in this study. 2 and 20 dynes/cm shear forces were defined as low and high intensities, respectively. A SCD-1 upregulation in human MG63 osteosarcoma cells under 20, but not 2, dynes/cm shear force stimulation was shown, and this induction was regulated by Smad1/5 and peroxisome proliferator-activated receptor δ (PPARδ) signaling. Moreover, gene knockdown of PPARδ and SCD-1 in human MG63 osteosarcoma cells attenuated the differentiation inhibition and resulted in much more cell death of high shear force initiation. The present study finds a possible auto-protective role of SCD-1 upregulation in high shear force-damaged human MG63 osteosarcoma cells. However, its detailed regulation in the cancer fate decision of high shear force should be further examined.
机械调节被认为是癌症进展和恶性肿瘤的重要调节剂。高剪切力已被发现抑制细胞周期进程，并导致各种癌细胞死亡。硬脂酰辅酶 A 去饱和酶（SCD）-1 是重要的脂肪生成酶之一，最近已被认为是癌症治疗的潜在药物靶点。在这项研究中，我们确定了剪切力刺激的细胞命运控制是否通过调节癌细胞中的 SCD-1 表达。本研究使用人 MG63 骨肉瘤细胞。2 和 20 达因/平方厘米的剪切力分别定义为低强度和高强度。结果显示，在 20 达因/平方厘米但不是 2 达因/平方厘米的剪切力刺激下，人 MG63 骨肉瘤细胞中的 SCD-1 上调，这种诱导受 Smad1/5 和过氧化物酶体增殖物激活受体 δ（PPARδ）信号调节。此外，人 MG63 骨肉瘤细胞中 PPARδ 和 SCD-1 的基因敲低减弱了分化抑制作用，并导致更多的高剪切力起始细胞死亡。本研究发现 SCD-1 上调在高剪切力损伤的人 MG63 骨肉瘤细胞中可能具有自我保护作用。然而，其在高剪切力下癌症命运决定中的详细调节仍需进一步研究。
