Calreticulin-driven autophagy enhances cell proliferation in laryngeal squamous cell carcinoma

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2024-11-04 DOI:10.1016/j.tice.2024.102603

Shufeng Gao, Xintao Wang, Yun Huang, Longgui You

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Abstract

Background

Calreticulin (CALR) is a multifunctional calcium-binding protein. Recent studies have revealed that CALR contributes to tumor development and promotes cancer cell proliferation. However, how CALR affects the development of laryngeal squamous cell carcinoma (LSCC) remains mysterious. Thus, this study aimed to explore the effect of CALR on LSCC development and uncover its underlying mechanisms.

Methods

CALR expression in LSCC cell lines and tissues was examined by qRT-PCR and western blot analysis and its functional role was detected via in vivo and in vitro assays. Cell proliferation was discriminated with CCK-8 and colony formation assays, while apoptosis was analyzed using flow cytometry. Autophagy levels were measured via LC3 immunofluorescence, and western blot assay was conducted to assess apoptosis- and autophagy-related proteins. Additionally, a mouse xenograft model was employed to determine the impact of CALR knockdown on tumor growth.

Results

We found that CALR knockdown reduced LSCC cell viability and proliferation while enhancing apoptosis, whereas CALR overexpression showed opposite effects. In vivo experiments verified that CALR knockdown suppressed tumor growth. In addition, elevated CALR expression induced autophagy in LSCC cells, while autophagy inhibitor 3-MA (2.5 mM) reversed the anti-apoptosis effects of CALR overexpression.

Conclusion

Our study identifies CALR as an oncogene in LSCC, where it promotes tumor progression by inducing autophagy and inhibiting apoptosis. Targeting CALR or modulating autophagy may represent novel therapeutic strategies for LSCC.

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钙网蛋白驱动的自噬可促进喉鳞状细胞癌细胞的增殖。

背景：钙网蛋白（CALR）是一种多功能钙结合蛋白。最近的研究发现，CALR有助于肿瘤发生和促进癌细胞增殖。然而，CALR如何影响喉鳞状细胞癌（LSCC）的发展仍是一个谜。因此，本研究旨在探讨CALR对LSCC发展的影响，并揭示其潜在机制：方法：通过qRT-PCR和Western印迹分析检测CALR在LSCC细胞系和组织中的表达，并通过体内和体外实验检测其功能作用。细胞增殖通过 CCK-8 和集落形成试验进行判别，细胞凋亡则通过流式细胞术进行分析。通过 LC3 免疫荧光法测定自噬水平，并进行 Western 印迹法评估凋亡和自噬相关蛋白。此外，还采用了小鼠异种移植模型来确定 CALR 敲除对肿瘤生长的影响：结果：我们发现，CALR敲除降低了LSCC细胞的活力和增殖，同时增强了细胞凋亡，而CALR过表达则表现出相反的效果。体内实验验证了 CALR 敲除抑制了肿瘤生长。此外，CALR表达的升高诱导了LSCC细胞的自噬，而自噬抑制剂3-MA（2.5 mM）逆转了CALR过表达的抗凋亡效应：我们的研究发现，CALR是LSCC中的一种癌基因，它通过诱导自噬和抑制细胞凋亡来促进肿瘤进展。靶向 CALR 或调节自噬可能是 LSCC 的新型治疗策略。

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

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.