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01-03-2018 | Endocrine Tumors

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

Authors: Anna Aronova, MD, Irene M. Min, PhD, Michael J. P. Crowley, MS, Suraj J. Panjwani, MBBS, Brendan M. Finnerty, MD, Theresa Scognamiglio, MD, Yi-Fang Liu, Timothy G. Whitsett, PhD, Shipra Garg, MD, Michael J. Demeure, MD, Olivier Elemento, PhD, Rasa Zarnegar, MD, Thomas J. Fahey III, MD

Published in: Annals of Surgical Oncology | Issue 3/2018

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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Title: STMN1 is Overexpressed in Adrenocortical Carcinoma and Promotes a More Aggressive Phenotype In Vitro
Authors: Anna Aronova, MD
Irene M. Min, PhD
Michael J. P. Crowley, MS
Suraj J. Panjwani, MBBS
Brendan M. Finnerty, MD
Theresa Scognamiglio, MD
Yi-Fang Liu
Timothy G. Whitsett, PhD
Shipra Garg, MD
Michael J. Demeure, MD
Olivier Elemento, PhD
Rasa Zarnegar, MD
Thomas J. Fahey III, MD
Publication date: 01-03-2018
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue 3/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-017-6296-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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