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

IF 9.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cellular & Molecular Biology Letters Pub Date : 2024-09-27 DOI:10.1186/s11658-024-00639-w

Yao Zhang, Chenglong Wang, Yitong Xu, Hongbo Su

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引用次数: 0

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.

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Tetraspanin 3通过调节β1整合素细胞内循环促进NSCLC细胞增殖。

背景：四泛素参与癌症的发生和发展已被广泛关注。本研究探讨了四泛素 3（TSPAN3）在非小细胞肺癌（NSCLC）细胞中的功能和分子机制：方法：通过免疫组化、Western 印迹和实时聚合酶链反应（PCR）对确诊为 NSCLC 患者的组织样本进行分析，以确定 TSPAN3 在癌症进展中的参与情况。同时，我们还利用 A549 和 H460 细胞，通过免疫印迹、实时聚合酶链反应、免疫荧光染色、共沉淀、细胞增殖试验和硝唑（NZ）冲淡试验等多种方法，在体外进行了详尽的机理研究。本研究在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高表达。此外，TSPAN3的高水平与NSCLC患者的分化不良、淋巴结受累、晚期病理肿瘤-结节-转移分期和预后不良呈正相关。TSPAN3 具有促进 NSCLC 细胞体外和体内增殖的潜力。具体而言，研究发现TSPAN3通过LEL结构域与β1整合素相互作用，从而促进β1整合素分选到Rab11a内体，并促进β1整合素的再循环和上调：我们的研究结果表明，TSPAN3可能是治疗NSCLC的一个有价值的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular & Molecular Biology Letters 生物-生化与分子生物学

CiteScore

11.60

自引率

13.30%

发文量

101

审稿时长

3 months

期刊介绍： Cellular & Molecular Biology Letters is an international journal dedicated to the dissemination of fundamental knowledge in all areas of cellular and molecular biology, cancer cell biology, and certain aspects of biochemistry, biophysics and biotechnology.