Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
Department of Nursing, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
Clin Sci (Lond). 2022 Jun 17;136(11):895-909. doi: 10.1042/CS20220128.
Changes to some Golgi subfamily member proteins are reported to be involved in tumor metastasis. However, the functional role and potential mechanism of the Golgi A8 family member B (GOLGA8B) in lung squamous cell carcinoma (LUSC) remains unknown. In the present study, GOLGA8B expression was detected using qRT-PCR, Western blot, and immunohistochemistry (IHC). In vivo animal experiments and in vitro functional assays were performed to explore the function of GOLGA8B in LUSC. Luciferase assays were performed to investigate the underlying targets of GOLGA8B in LUSC. GOLGA8B was shown to be highly expressed in LUSC metastasis tissue, and significantly associated with the distant metastasis-free survival of LUSC patients. Loss-of-function assays indicated that silencing GOLGA8B suppressed LUSC cell tumorigenesis in vivo and weakened in vitro invasion and migration. GOLGA8B silencing-induced inhibition of invasion and migration was associated with the inactivation of STAT3 signaling. Importantly, these results showed that the number of circulating tumor cells (CTCs) was markedly higher in the GOLGA8B silencing group than in the control vector group. GOLGA8B expression was positively associated with p-STAT3 expression in LUSC tissue. Study findings revealed a novel mechanism by which GOLGA8B promotes tumor metastasis in LUSC cells and suggests that this protein could be a promising target for antitumor metastasis therapy in LUSC patients.
有报道称,一些高尔基亚家族成员蛋白的改变与肿瘤转移有关。然而,高尔基 A8 家族成员 B(GOLGA8B)在肺鳞状细胞癌(LUSC)中的功能作用和潜在机制尚不清楚。在本研究中,使用 qRT-PCR、Western blot 和免疫组织化学(IHC)检测 GOLGA8B 的表达。进行体内动物实验和体外功能测定,以探讨 GOLGA8B 在 LUSC 中的功能。进行荧光素酶测定以研究 GOLGA8B 在 LUSC 中的潜在靶标。结果显示,GOLGA8B 在 LUSC 转移组织中高表达,与 LUSC 患者的无远处转移生存显著相关。功能丧失实验表明,沉默 GOLGA8B 抑制了 LUSC 细胞体内的肿瘤发生,并减弱了体外侵袭和迁移。GOLGA8B 沉默诱导的侵袭和迁移抑制与 STAT3 信号的失活有关。重要的是,这些结果表明,在 GOLGA8B 沉默组中循环肿瘤细胞(CTC)的数量明显高于对照组。GOLGA8B 表达与 LUSC 组织中 p-STAT3 表达呈正相关。研究结果揭示了 GOLGA8B 促进 LUSC 细胞肿瘤转移的新机制,并表明该蛋白可能成为 LUSC 患者抗肿瘤转移治疗的有前途的靶点。