溶质载体家族39成员14通过磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路促进食管鳞状细胞癌的发展。

SLC39A14 promotes the development of esophageal squamous cell carcinoma through PI3K/Akt/mTOR signaling pathway.

作者信息

Qu Hangshuai, Yu Qingxin, Ye Luxia, Zheng Jingmin

机构信息

Department of Public Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang Province, China.

Department of pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo City, Zhejiang Province, China.

出版信息

Int Immunopharmacol. 2025 Jan 27;146:113831. doi: 10.1016/j.intimp.2024.113831. Epub 2024 Dec 18.

DOI:10.1016/j.intimp.2024.113831

PMID:39700956

Abstract

OBJECTIVES

This study aims to investigate the expression of solute carrier family 39 member 14 (SLC39A14) in esophageal squamous cell carcinoma (ESCC) tissues and its prognosis, as well as the impact of SLC39A14 expression on the biological behavior of ESCC cells and associated mechanisms.

METHODS

Bioinformatics analysis was utilized to compare the differential expression of SLC39A14 mRNA between esophageal cancer tissues and adjacent non-cancerous tissues. Immunohistochemistry was employed to evaluate SLC39A14 protein expression in human ESCC tissues and normal esophageal tissues, followed by an analysis of its association with clinicopathological parameters in esophageal cancer patients. Through cell proliferation, migration, invasion, and Western blot assays, we deeply evaluated the specific effects of SLC39A14 gene knockdown (or overexpression) on ESCC cells and explored its potential biological functions in ESCC. Subsequently, we validated the role of SLC39A14 in ESCC in a xenograft model. Furthermore, LY294002 drug intervention was used to verify the regulatory effect of SLC39A14 on PI3K/Akt/mTOR signaling pathway.

RESULTS

Both mRNA and protein levels of SLC39A14 were significantly elevated in tumor tissues from ESCC patients compared to adjacent normal tissues. Notably, higher levels of SLC39A14 expression positively correlated with ESCC tumor size (p = 0.010) and clinical T stage (p = 0.025), while exhibiting a negative correlation with overall patient survival rates (p = 0.023). In vitro experiments demonstrated that knocking down SLC39A14 significantly inhibited cell proliferation, migration and invasion. In vivo study showed that SLC39A14 facilitated progression within murine models bearing ESCC tumors. Mechanistic analyses suggested that pro-carcinogenic effects exerted by SLC39A14 are mediated through activation of the PI3K/Akt/mTOR signaling pathway.

CONCLUSIONS

Our findings suggest that SLC39A14 may serve as a potential biomarker for ESCC due to its pro-oncogenic role during ESCC progression.

摘要

目的

本研究旨在探讨溶质载体家族39成员14（SLC39A14）在食管鳞状细胞癌（ESCC）组织中的表达及其预后情况，以及SLC39A14表达对ESCC细胞生物学行为的影响及相关机制。

方法

利用生物信息学分析比较食管癌组织与相邻非癌组织中SLC39A14 mRNA的差异表达。采用免疫组织化学法评估SLC39A14蛋白在人ESCC组织和正常食管组织中的表达情况，随后分析其与食管癌患者临床病理参数的相关性。通过细胞增殖、迁移、侵袭及蛋白质免疫印迹分析，我们深入评估了SLC39A14基因敲低（或过表达）对ESCC细胞的具体影响，并探讨了其在ESCC中的潜在生物学功能。随后，我们在异种移植模型中验证了SLC39A14在ESCC中的作用。此外，使用LY294002药物干预来验证SLC39A14对PI3K/Akt/mTOR信号通路的调节作用。

结果

与相邻正常组织相比，ESCC患者肿瘤组织中SLC39A14的mRNA和蛋白水平均显著升高。值得注意的是，较高水平的SLC39A14表达与ESCC肿瘤大小（p = 0.010）和临床T分期（p = 0.025）呈正相关，而与患者总体生存率呈负相关（p = 0.023）。体外实验表明，敲低SLC39A14可显著抑制细胞增殖、迁移和侵袭。体内研究表明，SLC39A14促进了携带ESCC肿瘤的小鼠模型中的肿瘤进展。机制分析表明，SLC39A14发挥的促癌作用是通过激活PI3K/Akt/mTOR信号通路介导的。