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瞬时受体电位香草酸亚型2(TRPV2)钙通道通过激活自噬促进乳腺癌进展潜能。

TRPV2 calcium channel promotes breast cancer progression potential by activating autophagy.

作者信息

Li Qing, Li Huixian, Zhu Ruiwen, Cho William Chi Shing, Yao Xiaoqiang, Leung Fung Ping, Tse Gary, Leung Lai Kwok, Wong Wing Tak

机构信息

School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong, 999077, China.

State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, 999077, China.

出版信息

Cancer Cell Int. 2024 Sep 27;24(1):324. doi: 10.1186/s12935-024-03506-y.

Abstract

Breast cancer, the most prevalent and aggressive tumor affecting women, requires identification of disease determinants to facilitate the development of effective therapeutic strategies. Transient receptor potential vanilloid 2 (TRPV2), an ion channel highly permeable for calcium (Ca), is implicated in physiological and pathological processes. Nevertheless, the role of TRPV2 in breast cancer remains poorly elucidated. In this study, we found high levels of TRPV2 expression associated with advanced malignancy, thereby suggesting its potential as a biomarker for breast cancer staging. We demonstrated that TRPV2 activation promotes breast cancer cell proliferation, migration, and invasion, while silencing of TRPV2 suppresses breast cancer progression, highlighting the oncogenic role of TRPV2. Moreover, we reveal that TRPV2 facilitates cancer progression by modulating the CaMKKβ/AMPK/ULK1-autophagic axis through mediating calcium influx, providing new insights into TRPV2 as a novel therapeutic target for breast cancer treatment.

摘要

乳腺癌是影响女性的最常见且侵袭性最强的肿瘤,需要识别疾病的决定因素以促进有效治疗策略的开发。瞬时受体电位香草酸亚型2(TRPV2)是一种对钙(Ca)具有高度通透性的离子通道,参与生理和病理过程。然而,TRPV2在乳腺癌中的作用仍未得到充分阐明。在本研究中,我们发现TRPV2的高表达水平与晚期恶性肿瘤相关,从而提示其作为乳腺癌分期生物标志物的潜力。我们证明,TRPV2激活促进乳腺癌细胞的增殖、迁移和侵袭,而TRPV2沉默则抑制乳腺癌进展,突出了TRPV2的致癌作用。此外,我们发现TRPV2通过介导钙内流调节CaMKKβ/AMPK/ULK1自噬轴,从而促进癌症进展,为将TRPV2作为乳腺癌治疗的新型治疗靶点提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06fc/11438410/d9b67c77f71e/12935_2024_3506_Fig1_HTML.jpg

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