Du Chun, Qi Zijuan, Zhang Wei
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, 150081, China.
Department of Pathology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang Province, 150000, China.
Curr Pharm Biotechnol. 2025;26(2):235-245. doi: 10.2174/0113892010259632240213091136.
Non-small cell lung cancer (NSCLC) is a type of malignant tumor with high morbidity as well as mortality. The process of lung cancer may be driven by cancer stem cells. It was known that MFAP5 enhanced the occurrence of diverse types of cancer. Also, MFAP5 has the potential to induce the degradation of FBW7 which is a tumor suppressor. Lower levels of FBW7 enhance the stability of Sox9, which is the cancer stem cell-related protein. However, whether the MFAP5 can modulate the stem cell features of NSCLC cells by modulating the FBW7/Sox9 axis is unclear. Therefore, this study aimed to explore the role of MFAP5/FBW7/Sox9 axis on the stem cell features of NSCLC cells and develop a new treatment of this carcinoma.
In this study, we explored the effects of MFAP5 on the stem cell features of NSCLC cells for the first time. We established MFAP5 overexpression and knockdown NSCLC cells. Clone formation assays and cell sphere culture assays were conducted for the exploration of the growth and stem cell features of these cells. Western blotting was applied for the detection of Sox9 and FBW7 expression in these cells. CHX was applied for the treatment of these cells for the detection of degradation of Sox9. Finally, we overexpressed the Sox9 in MFAP5 knockdown NSCLC cells.
MFAP5 promoted the growth and stem cell features of these cells. Knockdown of MFAP5 induced higher levels of FBW7 while restricting the expression of Sox9. Knockdown of MFAP5 aggravated the degradation of Sox9. Overexpression of Sox9 abrogated the efficacy of MFAP5 inhibition on the growth as well as stem cell features of these cells. The results of this study clarified the role of MFAP5/FBW7/Sox9 axis on the development of non-small cell lung cancer cells, providing the potential therapeutic target for the clinical treatment of NSCLC.
MFAP5 maintained the stem cell features of non-small cell lung cancer cells by modulating FBW7/Sox9 axis.
非小细胞肺癌（NSCLC）是一种发病率和死亡率都很高的恶性肿瘤。肺癌的发生过程可能由癌症干细胞驱动。已知MFAP5会促进多种类型癌症的发生。此外，MFAP5有诱导肿瘤抑制因子FBW7降解的潜力。FBW7水平降低会增强Sox9的稳定性，而Sox9是与癌症干细胞相关的蛋白。然而，MFAP5是否能通过调节FBW7/Sox9轴来调控NSCLC细胞的干细胞特性尚不清楚。因此，本研究旨在探讨MFAP5/FBW7/Sox9轴在NSCLC细胞干细胞特性中的作用，并开发针对这种癌症的新治疗方法。
在本研究中，我们首次探究了MFAP5对NSCLC细胞干细胞特性的影响。我们建立了MFAP5过表达和敲低的NSCLC细胞系。进行克隆形成试验和细胞球培养试验以探究这些细胞的生长和干细胞特性。应用蛋白质免疫印迹法检测这些细胞中Sox9和FBW7的表达。应用环己酰亚胺处理这些细胞以检测Sox9的降解情况。最后，我们在MFAP5敲低的NSCLC细胞中过表达Sox9。
MFAP5促进了这些细胞的生长和干细胞特性。敲低MFAP5会诱导更高水平的FBW7，同时抑制Sox9的表达。敲低MFAP5会加剧Sox9的降解。过表达Sox9消除了MFAP5抑制对这些细胞生长和干细胞特性的影响。本研究结果阐明了MFAP5/FBW7/Sox9轴在非小细胞肺癌细胞发展中的作用，为NSCLC的临床治疗提供了潜在的治疗靶点。
MFAP5通过调节FBW7/Sox9轴维持非小细胞肺癌细胞的干细胞特性。
