{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:17:44Z","timestamp":1792840664019,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swim Across America Foundation (AB and JP)"},{"name":"NIH\/NCI R21CA245609 (JP)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Bone metastasis of breast cancer results in severe bone loss, fractures, and death. Crosstalk between breast cancer cells and bone resident cells promotes osteoclast activity and the release of growth factors from the bone matrix resulting in aggressive tumor growth and bone loss. We and others have shown that Runt-related transcription factor-2 (Runx2) promotes metastatic tumor growth-associated bone loss. Breast cancer cells also induce autophagy to survive metabolic stress at the metastatic site. Recently, we reported a Runx2-dependent increase in autophagy. In this study, to examine the underlying mechanisms of metastasis and tumor resistance to stress, we used a bone metastatic isogenic variant of breast cancer MDA-MB-231 cells isolated from a xenograft tumor mouse model of metastasis. Our results with immunofluorescence and biochemical approaches revealed that Runx2 promotes microtubule (MT) stability to facilitate autophagy. Stable MTs are critical for autophagosome trafficking and display increased acetylation at Lysine 40 of \u03b1-tubulin. Runx2 silencing decreases acetylated \u03b1-tubulin levels. The expression levels of HDAC6 and \u03b1TAT1, which serve to regulate the acetylation of \u03b1-tubulin, were not altered with Runx2 silencing. We found that HDAC6 interaction with \u03b1-tubulin is inhibited by Runt-related factor-2 (Runx2). We show that the expression of wild-type Runx2 can restore the acetylated polymer of MTs in Runx2 knockdown cells, while the C-terminal deletion mutant fails to rescue the polymer of MTs. Importantly, cellular stress, such as glucose starvation also increases the acetylation of \u03b1-tubulin. We found that the loss of Runx2 increases the sensitivity of breast cancer cells to MT-targeting agents. Overall, our results indicate a novel regulatory mechanism of microtubule acetylation and suggest that Runx2 and acetylated microtubules may serve as therapeutic targets for bone metastatic tumors.<\/jats:p>","DOI":"10.3390\/cancers14143436","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"3436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Role of Runx2 in Microtubule Acetylation in Bone Metastatic Breast Cancer Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9995-1233","authenticated-orcid":false,"given":"Ahmad","family":"Othman","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507, Armour Academic Building, Chicago, IL 60612, USA"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Winogradzki","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507, Armour Academic Building, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1266-8599","authenticated-orcid":false,"given":"Shreya","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507, Armour Academic Building, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waddell","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507, Armour Academic Building, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2531-5976","authenticated-orcid":false,"given":"Alan","family":"Blank","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507, Armour Academic Building, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitesh","family":"Pratap","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507, Armour Academic Building, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA A Cancer J. 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