4-IPP, a selective MIF inhibitor, causes mitotic catastrophe in thyroid carcinomas

Autor: Ambra Vittoria Gualeni, Chiara C. Volpi, Maida De Bortoli, Elena Taverna, Claudio Caccia, Giacomo Manenti, Luca Varinelli, Italia Bongarzone, Valerio Leoni, Dario Caccia, Annunziata Gloghini
Přispěvatelé: Varinelli, L, Caccia, D, Volpi, C, Caccia, C, De Bortoli, M, Taverna, E, Gualeni, A, Leoni, V, Gloghini, A, Manenti, G, Bongarzone, I
Rok vydání: 2015
Předmět:
AMPK
Cancer Research
Indoles
Proteome
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Blotting
Western
Fluorescent Antibody Technique
Mitosis
Apoptosis
Biology
Immunoenzyme Techniques
Endocrinology
Tandem Mass Spectrometry
Biomarkers
Tumor
Tumor Cells
Cultured
otorhinolaryngologic diseases
medicine
Humans
Endoreduplication
Thyroid Neoplasms
Receptors
Immunologic
Macrophage Migration-Inhibitory Factors
Mitotic catastrophe
Cell Proliferation
Macrophage migration inhibitory factor
Cell growth
Carcinoma
Cell Cycle
CD44
4-IPP
Anaplastic thyroid carcinoma
Cell cycle
Carcinoma
Papillary
Intramolecular Oxidoreductases
Cytokine
Oncology
Thyroid Cancer
Papillary
Papillary thyroid carcinoma
CD74
Metabolome
oxysterols
sterols
cholesterol
fatty acids
organic acids
mass spectrometry
metabolomics
Cancer research
biology.protein
Chromatography
Liquid
Zdroj: Endocrine-Related Cancer. 22:759-775
ISSN: 1479-6821
1351-0088
DOI: 10.1530/erc-15-0299
Popis: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is over-expressed in several human neoplastic cells. When MIF binds its receptor (CD74) and co-receptor (CD44), it initiates signaling cascades that orchestrate cell proliferation and survival, and it can directly modulate the activity of AMPK. These activities indicate that MIF potentially regulates cell survival and metabolism. We found that MIF was primarily co-expressed with CD74 in 16 out of 23 papillary thyroid carcinoma (PTC) and in all the 27 available anaplastic thyroid carcinoma (ATC) biopsy samples. MIF and CD74 were co-expressed in TPC-1 and HTC-C3 cell lines. The selective MIF inhibitor, 4-iodo-6-phenylpyrimidine (4-IPP), blocked MIF/CD74 internalization, activated JNK, and dose-dependently inhibited proliferation inducing apoptosis and mitotic cell death. In two CD74-negative cell lines, NIM-1 and K1, 4-IPP treatment partially reduced proliferation. Coordinated MIF and CD74 expression appeared to confer in tumor cells the plasticity necessary to escape cell cycle regulation, metabolic changes, and stress conditions. MIF/CD74 signaling removal made cells susceptible to apoptosis and mitotic cell death. This finding suggests a possible avenue for targeting DNA endoreduplication, thus preventing the proliferation of therapy-resistant cell subpopulations. This study highlights MIF/CD74 axis as an important player in the biology of aggressive thyroid neoplasms.
Databáze: OpenAIRE
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