Oncotarget

Research Papers:

LMO1 functions as an oncogene by regulating TTK expression and correlates with neuroendocrine differentiation of lung cancer

Liqin Du, Zhenze Zhao, Milind Suraokar, Spencer S. Shelton, Xiuye Ma, Tzu-Hung Hsiao, John D. Minna, Ignacio Wistuba and Alexander Pertsemlidis _

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Oncotarget. 2018; 9:29601-29618. https://doi.org/10.18632/oncotarget.25642

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Abstract

Liqin Du1, Zhenze Zhao1, Milind Suraokar2, Spencer S. Shelton1, Xiuye Ma3, Tzu-Hung Hsiao4, John D. Minna5, Ignacio Wistuba2,6 and Alexander Pertsemlidis3,7

1Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas, USA

2Departments of Pathology and Thoracic/Head and Neck Medical Oncology, UT MD Anderson Cancer Center, Houston, Texas, USA

3Greehey Children’s Cancer Research Institute, UT Health Science Center at San Antonio, San Antonio, Texas, USA

4Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan

5Hamon Center for Therapeutic Oncology Research and Departments of Pharmacology and Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, Texas, USA

6Department of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, Texas, USA

7Departments of Pediatrics and Cell Systems & Anatomy, UT Health Science Center at San Antonio, San Antonio, Texas, USA

Correspondence to:

Liqin Du, email: liqindu6@txstate.edu

Alexander Pertsemlidis, email: pertsemlidis@uthscsa.edu

Keywords: LMO1; lung cancer; neuroendocrine; TTK

Received: February 07, 2017    Accepted: May 24, 2018    Published: July 03, 2018

ABSTRACT

LMO1 encodes a protein containing a cysteine-rich LIM domain involved in protein–protein interactions. Recent studies have shown that LMO1 functions as an oncogene in several cancer types, including non-small cell lung cancer (NSCLC). However, the function of LMO1 in other histological subtypes of lung cancer, such as small cell lung cancer (SCLC), was not investigated. In analyzing the expression of LMO1 across a panel of lung cell lines, we found that LMO1 expression levels were significantly and dramatically higher in SCLC cells, an aggressive neuroendocrine subtype of lung cancer, relative to NSCLC and normal lung cells. In NSCLC cells, LMO1 mRNA levels were significantly correlated with expression of neuroendocrine differentiation markers. Our in vitro investigations indicated that LMO1 had the general property of promoting cell proliferation in lung cancer cells representing different histological subtypes, suggesting a general oncogenic function of LMO1 in lung cancer. In investigating the clinical relevance of LMO1 as an oncogene, we found that a high tumor level of the LMO1 mRNA was an independent predictor of poor patient survival. These results suggest that LMO1 acts as an oncogene, with expression correlated with neuroendocrine differentiation of lung cancer, and that it is a determinant of lung cancer aggressiveness and prognosis. By combining gene expression correlations with patient survival and functional in vitro investigations, we further identified TTK as mediating the oncogenic function of LMO1 in lung cancer cells.


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