Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, NHC Key Laboratory of Biological Nanotechnology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, China.
Int J Biol Sci. 2022 Jan 1;18(3):1134-1149. doi: 10.7150/ijbs.68091. eCollection 2022.
Metastasis is the main cause of death in patients with nasopharyngeal carcinoma (NPC). The molecular mechanisms underlying the metastasis of NPC remain to be elucidated. TBL1X has been shown abnormally expressed in diverse cancers. However, the role and mechanism of TBL1X in NPC remain unknown. Here, we showed TBL1X expression was significantly higher in metastatic NPC tissues compared to non-metastatic tissues and significantly correlated with TNM stage and metastasis of NPC patients. In addition, NPC patients with high TBL1X expression had a poor prognosis. TBL1X interacted with TCF4 to trans-activate Flot2 expression. TBL1X promoted NPC cell migration and invasion in vitro and through Flot2. Moreover, Flot2 increased the expression of TBL1X by upregulating c-myc, which was identified to be a positively regulatory transcription factor of TBL1X. TBL1X could restore the functional changes of NPC cells resulting from Flot2 alteration. TBL1X and Flot2 were positively correlated in NPC. Patients with high expression of both TBL1X and Flot2 possessed poorer overall survival (OS) and disease-free survival (DFS) compared to patients with high expression of any single one of the two proteins. Our findings demonstrate that TBL1X and Flot2 positively regulate each other to promote NPC metastasis, which provides novel potential molecular targets for NPC treatment.
转移是鼻咽癌（NPC）患者死亡的主要原因。NPC 转移的分子机制仍有待阐明。TBL1X 在多种癌症中异常表达。然而，TBL1X 在 NPC 中的作用和机制尚不清楚。在这里，我们发现转移性 NPC 组织中 TBL1X 的表达明显高于非转移性组织，并且与 NPC 患者的 TNM 分期和转移明显相关。此外，TBL1X 高表达的 NPC 患者预后不良。TBL1X 与 TCF4 相互作用以反式激活 Flot2 的表达。TBL1X 促进 NPC 细胞在体外的迁移和侵袭，并通过 Flot2 促进 NPC 细胞的迁移和侵袭。此外，Flot2 通过上调 c-myc 增加 TBL1X 的表达，c-myc 被鉴定为 TBL1X 的正向调控转录因子。TBL1X 可以恢复 Flot2 改变导致的 NPC 细胞的功能变化。TBL1X 和 Flot2 在 NPC 中呈正相关。与仅高表达 TBL1X 或 Flot2 的患者相比，同时高表达 TBL1X 和 Flot2 的患者总生存期（OS）和无病生存期（DFS）更差。我们的研究结果表明，TBL1X 和 Flot2 相互正向调节，共同促进 NPC 的转移，为 NPC 的治疗提供了新的潜在分子靶点。
