四跨膜蛋白 3 通过调节β1 整合素细胞内再循环促进非小细胞肺癌细胞增殖。

Tetraspanin 3 promotes NSCLC cell proliferation via regulation of β1 integrin intracellular recycling.

机构信息

Department of Pathology, the First Hospital and Basic Medical Sciences College of China Medical University, Shenyang, 110001, China.

Department of Pain, the First Hospital of China Medical University, Shenyang, 110001, China.

出版信息

Cell Mol Biol Lett. 2024 Sep 27;29(1):124. doi: 10.1186/s11658-024-00639-w.

DOI:10.1186/s11658-024-00639-w

PMID:39333841

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11428915/

Abstract

BACKGROUND

The involvement of tetraspanins in cancer development has been widely implicated. In this study, the function and molecular mechanisms of tetraspanin 3 (TSPAN3) in non-small cell lung cancer (NSCLC) cells were explored.

METHODS

Tissue samples from patients diagnosed with NSCLC were analyzed by immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) to indicate the involvement of TSPAN3 in cancer progression. In the meantime, we also performed exhaustive mechanistic studies using A549 and H460 cells in vitro through a variety of methods including western blotting, real-time PCR, immunofluorescent staining, coimmunoprecipitation, cell proliferation assay, and nocodazole (NZ) washout assay. Proper statistical analysis was implemented wherever necessary in this study.

RESULTS

TSPAN3 was found to be highly expressed in lung cancer cells and tissues. Moreover, high levels of TSPAN3 positively correlated with poor differentiation, lymph node involvement, advanced pathological tumor-node-metastasis stage, and poor prognosis in patients with NSCLC. TSPAN3 showed potential to promote the proliferation of NSCLC cells in vitro and in vivo. Specifically, TSPAN3 was found to interact with β1 integrin via the LEL domain, thereby facilitating the sorting of β1 integrin into Rab11a endosomes and promoting β1 integrin recycling and upregulation.

CONCLUSIONS

Our findings reveal TSPAN3 may represent a potentially valuable therapeutic target for NSCLC.

摘要

背景

四跨膜蛋白家族成员在癌症的发生发展过程中发挥着重要作用。本研究旨在探讨四跨膜蛋白 3（TSPAN3）在非小细胞肺癌（NSCLC）细胞中的功能及其分子机制。

方法

采用免疫组化、Western blot 和实时 PCR 等方法分析 NSCLC 患者组织样本中 TSPAN3 的表达情况，探讨 TSPAN3 在肿瘤进展中的作用。同时，我们还通过Western blot、实时 PCR、免疫荧光染色、免疫共沉淀、细胞增殖实验和紫杉醇（NZ）洗脱实验等方法，在 A549 和 H460 细胞中进行了广泛的机制研究。本研究中，必要时进行了适当的统计分析。

结果

TSPAN3 在肺癌细胞和组织中呈高表达。此外，TSPAN3 高水平表达与 NSCLC 患者分化程度低、淋巴结转移、肿瘤-淋巴结-转移（TNM）分期晚和预后不良显著相关。TSPAN3 具有促进 NSCLC 细胞在体外和体内增殖的潜能。具体而言，TSPAN3 通过 LEL 结构域与β1 整合素相互作用，从而促进β1 整合素向 Rab11a 内涵体的分选，并促进β1 整合素的再循环和上调。