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TIAM2S发挥多方面作用,减轻放射敏感性、抑制细胞凋亡、促进细胞增殖并增强细胞迁移,从而加剧放射抗性增强的宫颈癌进展。

TIAM2S Operates Multifaced Talents to Alleviate Radiosensitivity, Restrict Apoptosis, Provoke Cell Propagation, and Escalate Cell Migration for Aggravating Radioresistance-Intensified Cervical Cancer Progression.

作者信息

Chuang Pei-Chin, Su Wen-Hong, Hsieh Ching-Hua, Huang Eng-Yen

机构信息

Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan.

Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807017, Taiwan.

出版信息

Cells. 2025 Feb 26;14(5):339. doi: 10.3390/cells14050339.

Abstract

Radioresistance remains a major obstacle in cervical cancer treatment, frequently engendering tumor relapse and metastasis. However, the details of its mechanism of action remain largely enigmatic. This study delineates the prospective impacts of short-form human T-cell lymphoma invasion and metastasis 2 (TIAM2S) involving the radiation resistance of cervical cancer. In this study, we established three pairs of radioresistant (RR) cervical cancer cells (HeLa, C33A and CaSki) and their parental wild-type (WT) cells. We revealed a consistent augmentation of , but not long-form human T-cell lymphoma invasion and metastasis 2 () were displayed in RR cells that underwent a 6 Gy radiation administration. Remarkably, RR cells exhibited decreased radiosensitivity and abridged apoptosis, as estimated through a clonogenic survival curve assay and Annexin V/Propidium Iodide apoptosis assay, respectively. TIAM2S suppression increased radiosensitivity and enhanced cell apoptosis in RR cells, whereas its forced introduction modestly abolished radiosensitivity and diminished WT cell apoptosis. Furthermore, TIAM2S overexpression notably aggravated RR cell migration, whereas its blockage reduced WT cell mobilities, as confirmed by an in vitro time-lapse recording assay. Notably, augmented lung localization was revealed after a tail-vein injection of CaSki-RR cells using the in vivo short-term lung locomotion nude mouse model. TIAM2S impediment notably reduced radioresistance-increased lung locomotion. This study provides evidence that TIAM2S may operate as an innovative signature in cervical cancer that is resistant to radiotherapy. It displays multi-faceted roles including radioprotection, restricting apoptosis, promoting cell proliferation, and escalating cell migration/metastasis. Targeting TIAM2S, together with conventional radiotherapy, may be an innovative strategy for intensifying radiosensitivity and protecting against subsequent uncontrolled tumor growth and metastasis in cervical cancer treatment.

摘要

放射抗性仍然是宫颈癌治疗中的一个主要障碍,常常导致肿瘤复发和转移。然而,其作用机制的细节在很大程度上仍然是个谜。本研究阐述了短型人类T细胞淋巴瘤侵袭和转移蛋白2(TIAM2S)对宫颈癌放射抗性的潜在影响。在本研究中,我们建立了三对放射抗性(RR)宫颈癌细胞系(HeLa、C33A和CaSki)及其亲代野生型(WT)细胞系。我们发现,在接受6 Gy辐射的RR细胞中,短型人类T细胞淋巴瘤侵袭和转移蛋白2(TIAM2S)呈现一致的增加,而长型人类T细胞淋巴瘤侵袭和转移蛋白2(TIAM2L)未出现增加。值得注意的是,通过克隆形成存活曲线分析和膜联蛋白V/碘化丙啶凋亡分析分别估计,RR细胞表现出放射敏感性降低和凋亡减少。TIAM2S抑制增加了RR细胞的放射敏感性并增强了细胞凋亡,而强制导入TIAM2S则适度消除了放射敏感性并减少了WT细胞的凋亡。此外,如体外延时记录分析所证实的,TIAM2S过表达显著加剧了RR细胞的迁移,而其阻断则降低了WT细胞的迁移能力。值得注意的是,使用体内短期肺部运动裸鼠模型,经尾静脉注射CaSki-RR细胞后,发现肺部定位增加。TIAM2S的阻断显著降低了放射抗性增加的肺部运动。本研究提供了证据表明TIAM2S可能作为宫颈癌中对放疗有抗性的一种新标志发挥作用。它发挥多方面的作用,包括放射保护、限制凋亡、促进细胞增殖以及加剧细胞迁移/转移。靶向TIAM2S并结合传统放疗,可能是一种在宫颈癌治疗中增强放射敏感性并防止随后肿瘤不受控制地生长和转移的创新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8c3/11898548/c52421ae1678/cells-14-00339-g001.jpg

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