ITF2 is a target of CXCR4 in MDA-MB-231 breast cancer cells and is associated with reduced survival in estrogen receptor-negative breast cancer

dc.contributor.authorAppaiah, Hitesh
dc.contributor.authorBhat-Nakshatri, Poornima
dc.contributor.authorMehta, Rutika
dc.contributor.authorThorat, Mangesh
dc.contributor.authorBadve, Sunil
dc.contributor.authorNakshatri, Harikrishna
dc.date.accessioned2019-03-29T20:58:02Z
dc.date.available2019-03-29T20:58:02Z
dc.date.issued2010-08-15
dc.descriptionRetrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040950/en_US
dc.description.abstractCXCR4, a chemokine receptor, plays an important role in breast cancer growth, invasion, and metastasis. The transcriptional targets of CXCR4 signaling are not known. Microarray analysis of CXCR4-enriched and CXCR4-low subpopulations of the MDA-MB-231 breast cancer cell line, which has a constitutively active CXCR4 signaling network, revealed differential expression of ∼ 200 genes in the CXCR4-enriched subpopulation. ITF2, upregulated in CXCR4-enriched cells, was investigated further. Expression array datasets of primary breast tumors revealed higher ITF2 expression in estrogen receptor negative tumors, which correlated with reduced progression free and overall survival and suggested its relevance in breast cancer progression. CXCL12, a CXCR4 ligand, increased ITF2 expression in MDA-MB-231 cells. ITF2 is a basic helixloop-helix transcription factor that controls the epithelial-to-mesenchymal transition and the function of the ID family (inhibitor-of-differentiation) of transcription factors, such as ID2. ID2 promotes differentiation of breast epithelial cells and its reduced expression in breast cancer is associated with an unfavorable prognosis. Both CXCR4 and ITF2 repressed ID2 expression. In xenograft studies, CXCR4-enriched cells formed large tumors and exhibited significantly elevated lung metastasis. Short interfering RNA against ITF2 reduced invasion of the CXCR4-enriched MDA-MB-231 subpopulation, whereas ITF2 overexpression restored the invasive capacity of MDA-MB-231 cells expressing CXCR4shRNA. Furthermore, overexpression of ITF2 in these cells enhanced tumor growth. We propose that ITF2 is one of the CXCR4 targets, which is involved in CXCR4-dependent tumor growth and invasion of breast cancer cells.en_US
dc.identifier.citationAppaiah, H., Bhat-Nakshatri, P., Mehta, R., Thorat, M., Badve, S., & Nakshatri, H. (2010). ITF2 is a target of CXCR4 in MDA-MB-231 breast cancer cells and is associated with reduced survival in estrogen receptor-negative breast cancer. Cancer Biology & Therapy, 10(6), 600–614. https://doi.org/10.4161/cbt.10.6.12586en_US
dc.identifier.doi10.4161/cbt.10.6.12586
dc.identifier.urihttps://hdl.handle.net/1805/18745
dc.language.isoen_USen_US
dc.publisherTaylor & Francisen_US
dc.subjectCXCR4en_US
dc.subjectbreast canceren_US
dc.subjectID2en_US
dc.subjectITF2Ben_US
dc.subjectinvasionen_US
dc.titleITF2 is a target of CXCR4 in MDA-MB-231 breast cancer cells and is associated with reduced survival in estrogen receptor-negative breast canceren_US
dc.typeArticleen_US
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