UNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system. However, emerging studies from both our and other laboratories support a role of UNC-45A outside of actomyosin regulation. This includes studies showing that UNC-45A: regulates gene transcription, co-localizes and biochemically co-fractionates with gamma tubulin and regulates centrosomal positioning, is found in the same subcellular fractions where MT-associated proteins are, and is a mitotic spindle-associated protein with MT-destabilizing activity in absence of the actomyosin system. Here, we extended our previous findings and show that UNC45A is variably expressed across a spectrum of cell lines with the highest level being found in HeLa cells and in ovarian cancer cells inherently paclitaxel-resistant. Furthermore, we show that UNC-45A is preferentially expressed in epithelial cells, localizes to mitotic spindles in clinical tumor specimens of cancer and co-localizes and co-fractionates with MTs in interphase cells independent of actin or myosin. In sum, we report alteration of UNC45A localization in the setting of chemotherapeutic treatment of cells with paclitaxel, and localization of UNC45A to MTs both in vitro and in vivo. These findings will be important to ongoing and future studies in the field that further identify the important role of UNC45A in cancer and other cellular processes.
|Original language||English (US)|
|Number of pages||10|
|Journal||Cancer biology & therapy|
|Early online date||Jul 22 2019|
|State||Published - Oct 3 2019|
Bibliographical noteFunding Information:
Department of Defense Ovarian Cancer Research Program Grant OC160377; the Minnesota Ovarian Cancer Alliance and the Randy Shaver Cancer Research and Community Fund grant; the Ovarian Cancer Research Fund Grant; the University of Minnesota Grand Challenges Grant; the Litman Family Fund for Cancer Research, Randy Shaver Cancer Research and Community Fund, Minnesota Masonic Charities, the Masonic Cancer Center (Grant # P30 CA77598) and Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Guillermo Marques (University of Minnesota Imaging Center) for assistance with image analysis. This work was supported by Department of Defense Ovarian Cancer Research Program Grant OC160377, the Minnesota Ovarian Cancer Alliance and the Randy Shaver Cancer Research and Community Fund grant to Martina Bazzaro, by the Ovarian Cancer Research Fund Grant to Boris Winterhoff and by the University of Minnesota Grand Challenges Grant to Tim Starr and Boris Winterhoff. Emil Lou is supported by the Litman Family Fund for Cancer Research, Randy Shaver Cancer Research and Community Fund, Minnesota Masonic Charities, the Masonic Cancer Center (Grant # P30 CA77598) and Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota to Emil Lou. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare no conflict of interests.
© 2019, © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
PubMed: MeSH publication types
- Journal Article
- Research Support, U.S. Gov't, Non-P.H.S.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
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