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Protein Kinase A (PKA), anchored to centrosomes, regulates a number of mitotic processes, though its role in maintaining centrosome integrity remains poorly understood. Here, we show that PKA is central to a signaling cascade involving the G protein-coupled estrogen receptor GPER1, which is essential for centrosome integrity in colon cancer cells. Activation of GPER1 by estrogens or a specific agonist triggers G\u03b1s protein-mediated stimulation of adenylyl cyclase, elevating cAMP levels and thereby increasing PKA activity. Excessive activation of GPER1-PKA leads to extra centrosomes with enlarged, displaced Centrin-2\n                    <jats:italic>foci<\/jats:italic>\n                    . Recruited to centrosomes by AKAP450, PKA phosphorylates Centrin-2, predominantly at aberrant centrioles and unexpectedly even outside of mitosis. These findings reveal a GPER1-PKA-Centrin signaling axis in CRC cells that regulates centrosome numbers and centriole integrity, shedding light on centrosome abnormalities that drive neoplastic transformation and tumor progression.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09249-4","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:31:29Z","timestamp":1764171089000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A GPER-PKA-Centrin axis regulates centrosome numbers and centriole integrity in colon cancer cells"],"prefix":"10.1038","volume":"8","author":[{"given":"Jeanine","family":"Fahrl\u00e4nder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"B\u00fchler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0738-9648","authenticated-orcid":false,"given":"Julia Martins","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catrin","family":"Zordick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madleen","family":"Busse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2671-9908","authenticated-orcid":false,"given":"Markus","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Sch\u00f6nfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8357-8160","authenticated-orcid":false,"given":"Ailine","family":"Stolz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"9249_CR1","doi-asserted-by":"publisher","first-page":"432","DOI":"10.3390\/cells11030432","volume":"11","author":"M Buhler","year":"2022","unstructured":"Buhler, M. & Stolz, A. 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