MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v10/MSV000098630/primaryOK200ProteomicsKevin D HoustonOrbitrap EclipseHomo Sapiens (ncbitaxon:9606)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=d75d887c0bc2421d95e23ec4416dc4bbkhouston@nmsu.eduNew Mexico State UniversityMassIVE115UNIMOD:21 - "Phosphorylation."While the contribution of the IGF-signaling axis in breast cancer is well-documented, the role of IGFBP-6 in breast carcinogenesis has not been extensively studied. In general, insulin-like growth factor binding protein-6 (IGFBP-6) sequesters insulin-like growth factor 2 (IGF-2) to attenuate activation of its cognate receptor IGF-1R. To reveal previously unknown mechanisms of breast cancer modulation by IGFBP-6 in breast cancer, proteomic analysis was performed in T47D cells after IGFBP-6 knockdown. Comparing protein expression and phosphosites after knockdown by unique siRNA sequences with a negative control and subsequent pathway analysis, a decrease in IGFBP-6 expression resulted in activation of interferon signaling pathways and a decrease in pathways involved in the G2/M cell cycle transition. A subset of the proteins identified in each cell regulatory pathway was validated by immunoblotting for specific proteins after IGFBP-6 knockdown. Cell cycle analysis showed that IGFBP-6 knockdown in Hormone Receptor Positive T47D breast cancer cells resulted in an increased number of cells in the G1 phase and a decrease in cells in G2, indicating a role for IGFBP-6 in cell cycle regulation. Knockdown of IGFBP-6 in a triple-negative breast cancer cell line, MDA-MB-231, also resulted in a decrease in Cyclin B1 accumulation, demonstrating that our observations are not cell line specific. Taken together, our results demonstrate that IGFBP-6 regulates cell cycle progression in breast cancer cells and interferon signaling in hormone-positive cells.IGFBP-6 regulates breast cancer cell cycle progression by promoting exit out of G1.Lariz Francisco J FJ, Hernandez Shayla S, Bautista-Tovar Diana C DC, Houston Kevin D KDfalseIGFBP-6 is a Regulator of Cell Cycle Progression by Promoting Exit Out of G1These data are for phosphoproteomic analysis of T47D Breast Cancer Cells treated with siRNA targeting IGFBP-6. Thu Jul 24 03:58:00 BST 2025MSV00009863041419198