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STMN1 is Overexpressed in Adrenocortical Carcinoma and Promotes a More Aggressive Phenotype In Vitro

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis and few therapeutic options. Stathmin1 (STMN1) is a cytosolic protein involved in microtubule dynamics through inhibition of tubulin polymerization and promotion of microtubule depolymerization, which has been implicated in carcinogenesis and aggressive behavior in multiple epithelial malignancies. We aimed to evaluate expression of STMN1 in ACC and to elucidate how this may contribute to its malignant phenotype.

Methods

STMN1 was identified by RNA sequencing as a highly differentially expressed gene in human ACC samples compared with benign adrenal tumors. Expression was confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical (IHC) staining of a tissue microarray (TMA) from two independent cohorts. The biologic relevance of STMN1 was investigated in NCI-H295R cells by lentivirus-mediated silencing.

Results

Differential gene expression demonstrated an eightfold increase in STMN1 messenger RNA (mRNA) in malignant compared with benign adrenal tissue. IHC showed significantly higher expression of STMN1 protein in ACC compared with normal and benign tissues. STMN1 knockdown in an ACC cell line resulted in decreased cell viability, cell-cycle arrest at G0/G1, and increased apoptosis in serum-starved conditions compared with scramble short hairpin RNA (shRNA) controls. STMN1 knockdown also decreased migration, invasion, and anchorage-independent growth compared with controls.

Conclusions

STMN1 is overexpressed in human ACC samples, and knockdown of this target in vitro resulted in a less aggressive phenotype of ACC, particularly under serum-starved conditions. Further study is needed to investigate the feasibility of interfering with STMN1 as a potential therapeutic target.

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Funding

This study was supported by the Weill Cornell Clinical and Translational Science Center NIH/NCATS Grant TL1TR000459.

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Authors and Affiliations

  1. Department of Surgery, Weill Cornell Medical Center, New York Presbyterian Hospital, New York, NY, USA

    Anna Aronova MD, Irene M. Min PhD, Michael J. P. Crowley MS, Suraj J. Panjwani MBBS, Brendan M. Finnerty MD, Rasa Zarnegar MD & Thomas J. Fahey III MD

  2. Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York Presbyterian Hospital, New York, NY, USA

    Theresa Scognamiglio MD & Yi-Fang Liu

  3. Translational Genomics Research Institute, Phoenix, AZ, USA

    Timothy G. Whitsett PhD, Shipra Garg MD & Michael J. Demeure MD

  4. Department of Physiology and Biophysics, Weill Cornell Medical Center, New York Presbyterian Hospital, New York, NY, USA

    Olivier Elemento PhD

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  1. Anna Aronova MD
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  2. Irene M. Min PhD
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Correspondence to Anna Aronova MD.

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Aronova, A., Min, I.M., Crowley, M.J.P. et al. STMN1 is Overexpressed in Adrenocortical Carcinoma and Promotes a More Aggressive Phenotype In Vitro. Ann Surg Oncol 25, 792–800 (2018). https://doi.org/10.1245/s10434-017-6296-2

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  • DOI: https://doi.org/10.1245/s10434-017-6296-2

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