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Expression of concern Free access | 10.1172/JCI122301

ATP11B mediates platinum resistance in ovarian cancer

Myrthala Moreno-Smith, J.B. Halder, Paul S. Meltzer, Tamas A. Gonda, Lingegowda S. Mangala, Rajesha Rupaimoole, Chunhua Lu, Archana S. Nagaraja, Kshipra M. Gharpure, Yu Kang, Cristian Rodriguez-Aguayo, Pablo E. Vivas-Mejia, Behrouz Zand, Rosemarie Schmandt, Hua Wang, Robert R. Langley, Nicholas B. Jennings, Cristina Ivan, Jeremy E. Coffin, Guillermo N. Armaiz, Justin Bottsford-Miller, Sang Bae Kim, Margaret S. Halleck, Mary J.C. Hendrix, William Bornman, Menashe Bar-Eli, Ju-Seog Lee, Zahid H. Siddik, Gabriel Lopez-Berestein, and Anil K. Sood

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Published May 29, 2018 - More info

Published in Volume 128, Issue 7 on July 2, 2018
J Clin Invest. 2018;128(7):3199–3199. https://doi.org/10.1172/JCI122301.
Copyright © 2018, American Society for Clinical Investigation
Published May 29, 2018 - Version history
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Related article:

ATP11B mediates platinum resistance in ovarian cancer
Myrthala Moreno-Smith, … , Gabriel Lopez-Berestein, Anil K. Sood
Myrthala Moreno-Smith, … , Gabriel Lopez-Berestein, Anil K. Sood
Research Article

ATP11B mediates platinum resistance in ovarian cancer

Abstract

Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. We found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhances the export of cisplatin from cells. The colocalization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins, such as syntaxin-6 (STX6) and vesicular-associated membrane protein 4 (VAMP4), strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, inhibition of ATP11B expression could serve as a therapeutic strategy to overcome cisplatin resistance.

Authors

Myrthala Moreno-Smith, J.B. Halder, Paul S. Meltzer, Tamas A. Gonda, Lingegowda S. Mangala, Rajesha Rupaimoole, Chunhua Lu, Archana S. Nagaraja, Kshipra M. Gharpure, Yu Kang, Cristian Rodriguez-Aguayo, Pablo E. Vivas-Mejia, Behrouz Zand, Rosemarie Schmandt, Hua Wang, Robert R. Langley, Nicholas B. Jennings, Cristina Ivan, Jeremy E. Coffin, Guillermo N. Armaiz, Justin Bottsford-Miller, Sang Bae Kim, Margaret S. Halleck, Mary J.C. Hendrix, William Bornman, Menashe Bar-Eli, Ju-Seog Lee, Zahid H. Siddik, Gabriel Lopez-Berestein, Anil K. Sood

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Original citation: J Clin Invest. 2013;123(5):2119–2130. https://doi.org/10.1172/JCI65425

Citation for this expression of concern: J Clin Invest. 2018;128(7):3199. https://doi.org/10.1172/JCI122301

The Editors recently became aware that Figure 3B appears to use a set of images that were previously published in a 2009 Clinical Cancer Research paper with different sample labels (doi: 10.1158/1078-0432.CCR-08-2306). Additionally, the empty liposome and control siRNA PCNA–stained panels appear to be the same. The Editorial Board is pursuing further investigation of this matter, and we will inform our readers of the outcome when the investigation is complete.

Footnotes

See the related article at ATP11B mediates platinum resistance in ovarian cancer.

Version history
  • Version 1 (May 29, 2018): Electronic publication
  • Version 2 (July 2, 2018): Print issue publication
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