Co-expression of galectin-3 and vimentin in triple negative breast cancer cells promotes tumor progression, metastasis and survival.

Q3 Biochemistry, Genetics and Molecular Biology Tumor Biology Pub Date : 2023-01-01 DOI:10.3233/TUB-230002
T Jeethy Ram, Asha Lekshmi, Pramod Darvin, Prakash Rajappan, K M Jagathnath Krishna, T M Anoop, Paul Augustine, Arun Peter Mathew, Kurian Cherian, Rexeena V Bhargavan, Thara Somanathan, M Radhakrishna Pillai, T R Santhosh Kumar, K Sujathan
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引用次数: 1

Abstract

Background: Lack of druggable targets and complex expression heterogeneity of known targets is common among TNBC subtypes. An enhanced expression of galectin-3 in TNBCs has already been documented. We have observed a tumor progression-dependent galectin-3 expression in TNBCs compared to adjacent epithelium and non TNBCs.

Objective: To unravel the association of galectin- 3 in tumor progression, aggressiveness and drug resistance in TNBC patients.

Methods: Galectin-3 expression in 489 breast cancer tissues was correlated with clinicopathological features and the results were validated in cell lines and mouse model by silencing galectin-3 using shRNA and the proteins were profiled by western blot and qRT-PCR. Protein interaction was analyzed by GFP Trap and Mass spectrometry.

Results: Galectin-3 expression correlated with tumor stage in TNBC and a lower galectin-3 expression was associated with poor patient survival. The positive correlation between galectin-3, vimentin and CD44 expression, pinpoints galectin-3 contribution to epithelial to mesenchymal transition, drug resistance and stemness. Vimentin was found as an interacting partner of galectin-3. Duplexing of galecin-3 and vimentin in patient samples revealed the presence of tumor cells co-expressing both galectin-3 and vimentin. In vitro studies also showed its role in tumor cell survival and metastatic potential, elementary for tumor progression. In vivo studies further confirmed its metastatic potential.

Conclusions: Tumor progression dependent expression pattern of galectin 3 was found to indicate prognosis. Co-expression of galectin-3 and vimentin in tumor cells promotes tumor dissemination, survival and its metastatic capability in TNBCs.

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半乳糖凝集素-3和波形蛋白在三阴性乳腺癌细胞中的共同表达促进肿瘤的进展、转移和生存。
背景:缺乏可药物靶点和已知靶点的复杂表达异质性在TNBC亚型中很常见。半凝集素-3在tnbc中的表达增强已被证实。与邻近上皮和非tnbc相比,我们已经观察到tnbc中肿瘤进展依赖性的半凝集素-3表达。目的:探讨凝集素- 3与TNBC患者肿瘤进展、侵袭性及耐药的关系。方法:在489例乳腺癌组织中,半乳糖凝集素-3的表达与临床病理特征相关,采用shRNA沉默半乳糖凝集素-3,在细胞系和小鼠模型上验证结果,并采用western blot和qRT-PCR对蛋白进行分析。用GFP Trap和质谱分析蛋白相互作用。结果:半乳糖凝集素-3表达与TNBC肿瘤分期相关,低半乳糖凝集素-3表达与患者生存差相关。半乳糖凝集素-3、vimentin与CD44表达呈正相关,明确了半乳糖凝集素-3在上皮向间质转化、耐药和干性中的作用。Vimentin被发现是半乳糖凝集素-3的相互作用伙伴。患者样本中半乳糖凝集素-3和vimentin的双工显示肿瘤细胞同时表达半乳糖凝集素-3和vimentin。体外研究也显示了它在肿瘤细胞存活和转移潜能中的作用,这是肿瘤进展的基础。体内研究进一步证实了其转移潜力。结论:肿瘤进展依赖于凝集素3的表达模式提示预后。半乳糖凝集素-3和vimentin在肿瘤细胞中的共同表达促进肿瘤在tnbc中的传播、存活及其转移能力。
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来源期刊
Tumor Biology
Tumor Biology 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
18
审稿时长
1 months
期刊介绍: Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Specific topics of interest include, but are not limited to: Pathway analyses, Non-coding RNAs, Circulating tumor cells, Liquid biopsies, Exosomes, Epigenetics, Cancer stem cells, Tumor immunology and immunotherapy, Tumor microenvironment, Targeted therapies, Therapy resistance Cancer genetics, Cancer risk screening. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines. The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication. Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).
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