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Endocrinol."],"abstract":"<jats:p>Insulin-like growth factor binding protein-6 (IGFBP-6) is induced by progesterone in breast cancer cells and regulates progesterone receptor (PR) via negative feedback. To further understand the mechanisms by which IGFBP-6 regulates PR and downstream signaling, proteomic analysis was performed in progesterone-treated T47D breast cancer cells following siRNA-mediated knockdown of IGFBP-6. Of the 8638 unique proteins identified, 29 proteins were downregulated, and 14 proteins were upregulated by progesterone treatment after IGFBP-6 knockdown. The decreased proteins were mostly identified as regulators of G2\/M phase of the cell cycle. SH2D4A is induced by progesterone only when IGFBP-6 was high. To understand the role of SH2D4A in progesterone-induced signaling, SH2D4A was knocked down using siRNA prior to progesterone treatment. Knockdown of IGFBP-6 or SH2D4A leads to cell cycle arrest in G1, and both SH2D4A and IGFBP-6 regulate cyclin B. Treatment of cells with abemaciclib and nocodazole caused cell cycle arrest in G1 and G2\/M, respectively, and decreased IGFBP-6, suggesting that IGFBP-6 is regulated in a cell cycle-dependent manner. These results identify a pathway linking progesterone to IGFBP-6 and SH2D4A, and to cell cycle progression in breast cancer cells.<\/jats:p>","DOI":"10.3389\/fendo.2026.1856096","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:24:36Z","timestamp":1782793476000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IGFBP-6 regulates SH2D4A expression to promote breast cancer cell cycle progression in response to progesterone"],"prefix":"10.3389","volume":"17","author":[{"given":"Francisco J.","family":"Lariz","sequence":"first","affiliation":[{"name":"New Mexico State University","place":["Las Cruces, NM, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana C.","family":"Bautista-Tovar","sequence":"additional","affiliation":[{"name":"New Mexico State University","place":["Las Cruces, NM, United 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