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.
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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