Yang Hang, Xiong Rong, Zhang Ruolan, Sun Shan, Pan Yingjie, Zhao Quanneng, Bie Jun, Luo Yi, Song Guiqin, Liu Kang
Institute of Tissue Engineering and Stem Cells, Beijing Anzhen Nanchong Hospital of Capital Medical University, Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, China.
Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, China.
Mol Carcinog. 2025 Apr;64(4):756-768. doi: 10.1002/mc.23885. Epub 2025 Jan 21.
Esophageal squamous cell carcinoma (ESCC) is prone to metastasis and is a leading cause of mortality. The cytoskeleton is closely related to cell morphology and movement; however, little research has been conducted on ESCC metastasis. In this study, we found that the anchoring filament protein ladinin 1 (LAD1) specifically binds to LINC01305 for co-regulating the level of modulating cortactin proteins (CTTN) and neuronal Wiskott-Aldrich syndrome protein (N-WASP) phosphorylation, which mediates cytoskeletal reorganization and affects the metastasis of ESCC cells. Additionally, LINC01305 and LAD1 jointly promoted the epithelial-mesenchymal transition (EMT) process by activating the phosphoinositide-3-kinase-protein kinase B (PI3K/AKT) signaling pathway. Moreover, LINC01305 and LAD1 were related to the late clinical stage and lymph node metastasis of ESCC. Our study demonstrated that LINC01305 and LAD1 are major determinants of ESCC dissemination and revealed a novel molecular mechanism of cytoskeletal reorganization that controls ESCC metastasis. Trial Registration: N/A.
食管鳞状细胞癌（ESCC）易于转移，是主要的死亡原因。细胞骨架与细胞形态和运动密切相关；然而，关于ESCC转移的研究很少。在本研究中，我们发现锚定丝蛋白拉迪宁1（LAD1）特异性结合LINC01305，共同调节调节皮质肌动蛋白（CTTN）和神经元韦斯科特-奥尔德里奇综合征蛋白（N-WASP）磷酸化水平，介导细胞骨架重组并影响ESCC细胞的转移。此外，LINC01305和LAD1通过激活磷酸肌醇-3-激酶-蛋白激酶B（PI3K/AKT）信号通路共同促进上皮-间质转化（EMT）过程。此外，LINC01305和LAD1与ESCC的临床晚期和淋巴结转移有关。我们的研究表明，LINC01305和LAD1是ESCC扩散的主要决定因素，并揭示了一种控制ESCC转移的细胞骨架重组新分子机制。试验注册：无。
