Lipocalin-2 inhibits pancreatic cancer stemness via the AKT/c-Jun pathway.

IF 4.3 3区生物学 Human Cell Pub Date : 2022-09-01 Epub Date: 2022-07-06 DOI:10.1007/s13577-022-00735-z

Peipei Hao, Jiamin Zhang, Shu Fang, Miaomiao Jia, Xian Xian, Sinan Yan, Yunpeng Wang, Qian Ren, Fengming Yue, Huixian Cui

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引用次数: 1

Abstract

Cancer stem cells (CSCs) are involved in cancer recurrence and metastasis owing to their self-renewal properties and drug-resistance capacity. Lipocalin-2 (Lcn2) of the lipocalin superfamily is highly expressed in pancreatic cancer. Nevertheless, reports on the involvement of Lcn2 in the regulation of pancreatic CSC properties are scant. This study is purposed to investigate whether Lcn2 plays a crucial role in CSC renewal and stemness maintenance in pancreatic carcinoma. Immunohistochemistry results of tumor tissue chips together with Gene Expression Omnibus sequencing files confirmed that Lcn2 is highly expressed in pancreatic carcinoma compared with that in normal tissues. The exogenous expression of Lcn2 attenuated CSC-associated SOX2, CD44, and EpCAM expression and suppressed sarcosphere formation and tumorigenesis in the pancreatic carcinoma cell line PANC-1, which showed low expression of Lcn2. However, Lcn2 knockout in BxPC-3 cell line, which presented high Lcn2 expression, promoted CSC stemness, further enhancing sarcosphere formation and tumorigenesis. Moreover, Lcn2 was found to regulate stemness in pancreatic cancer depending on the activation of AKT and c-Jun. Lcn2 suppresses stemness properties in pancreatic carcinoma by activating the AKT-c-Jun pathway, and thus, it may be a novel candidate to suppress the stemness of pancreatic cancer. This study provides a new insight into disease progression.

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脂联素-2通过AKT/c-Jun通路抑制胰腺癌干性。

癌症干细胞（CSCs）具有自我更新特性和抗药性，因此参与了癌症的复发和转移。脂联素超家族中的脂联素-2（Lcn2）在胰腺癌中高度表达。然而，有关 Lcn2 参与调控胰腺癌 CSC 特性的报道却很少。本研究旨在探讨Lcn2是否在胰腺癌CSC更新和干性维持中发挥关键作用。肿瘤组织芯片的免疫组化结果和基因表达总库测序文件证实，与正常组织相比，Lcn2在胰腺癌中高表达。在 Lcn2 低表达的胰腺癌细胞系 PANC-1 中，外源表达 Lcn2 可减轻与 CSC 相关的 SOX2、CD44 和 EpCAM 的表达，抑制肉泡形成和肿瘤发生。然而，在 Lcn2 高表达的 BxPC-3 细胞系中敲除 Lcn2 会促进 CSC 干性，进一步增强肌层形成和肿瘤发生。此外，研究还发现Lcn2能调节胰腺癌的干性，这取决于AKT和c-Jun的激活。Lcn2通过激活AKT-c-Jun通路抑制胰腺癌的干性特性，因此，它可能是抑制胰腺癌干性的一种新的候选物质。这项研究为疾病进展提供了新的视角。

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来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.