Zang Leilei, Song Yanmei, Tian Yanhua, Hu Ning
Department 5 of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050005, Hebei, China.
Department of Infection Management/Public Health, Hebei People's Hospital, Shijiazhuang, 050057, Hebei, China.
Heliyon. 2023 Oct 14;9(10):e20461. doi: 10.1016/j.heliyon.2023.e20461. eCollection 2023 Oct.
Papillary thyroid carcinoma (PTC) limits effective biomarkers for predicting prognosis and targeted therapy. Phosphatase and actin regulator 1 (PHACTR1) is a mobility-promoting molecule due to its regulation on F-actin formation, which is valuable for the investigation of PTC. Our study aimed to investigate the relationship between PHACTR1 and PTC carcinogenesis, especially mobility. Our results displayed that PHACTR1 expression was elevated in metastatic or larger PTC tissues. In addition, PTC cells K1 with more obvious mobility had higher PHACTR1 expression whereas weakly mobile cells TPC-1 was contrary. Moreover, PHACTR1 silencing inhibited the invasion, migration and tumorigenicity of K1 cells, while PHACTR1 overexpression promoted the invasion, migration and tumorigenicity in TPC-1 cells. Furthermore, PHACTR1 overexpression increased the fluorescent intensity of F-actin in TPC-1 cells. Importantly, the enhanced invasion and migration in TPC-1 cells caused by PHACTR1 overexpression were significantly reversed by the disruption of F-actin assembly with swinholide A. In conclusion, PHACTR1 can promote the mobility of PTC cells, which results in the carcinogenesis of PTC. PHACTR1-regulated F-actin formation determines the mobility of PTC cells. Therefore, PHACTR1 can function as a potential biomarker for predicting prognosis and targeting therapy in PTC.
甲状腺乳头状癌（PTC）缺乏有效的生物标志物来预测预后和指导靶向治疗。磷酸酶与肌动蛋白调节因子1（PHACTR1）是一种促进细胞迁移的分子，因其对F-肌动蛋白形成的调节作用，对PTC的研究具有重要价值。本研究旨在探讨PHACTR1与PTC发生发展尤其是细胞迁移之间的关系。我们的研究结果显示，在转移性或较大的PTC组织中，PHACTR1表达升高。此外，迁移能力更强的PTC细胞K1中PHACTR1表达较高，而迁移能力较弱的细胞TPC-1则相反。此外，沉默PHACTR1可抑制K1细胞的侵袭、迁移和致瘤性，而过表达PHACTR1则可促进TPC-1细胞的侵袭、迁移和致瘤性。此外，过表达PHACTR1可增加TPC-1细胞中F-肌动蛋白的荧光强度。重要的是，用鬼笔环肽A破坏F-肌动蛋白组装可显著逆转PHACTR1过表达引起的TPC-1细胞侵袭和迁移增强。总之，PHACTR1可促进PTC细胞的迁移，从而导致PTC的发生。PHACTR1调节的F-肌动蛋白形成决定了PTC细胞的迁移能力。因此，PHACTR1可作为预测PTC预后和靶向治疗的潜在生物标志物。
