LMO1 Functions as an Oncogene by Regulating TTK Expression and Correlates with Neuroendocrine Differentiation of Lung Cancer

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dc.contributor.authorDu, Liqin
dc.contributor.authorZhao, Zhenze
dc.contributor.authorSuraokar, Milind
dc.contributor.authorShelton, Spencer S.
dc.contributor.authorMa, Xiuye
dc.contributor.authorHsiao, Tzu-Hung
dc.contributor.authorMinna, John D.
dc.contributor.authorWistuba, Ignacio
dc.contributor.authorPertsemlidis, Alexander
dc.date.accessioned2019-08-26T13:29:07Z
dc.date.available2019-08-26T13:29:07Z
dc.date.issued2018-07
dc.description.abstractLMO1 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.
dc.description.departmentChemistry and Biochemistry
dc.formatText
dc.format.extent18 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationDu, L., Zhao, Z., Suraokar, M., Shelton, S. S., Ma, X., Hsiao, T. H., Minna, J. D., Wistuba, I., & Pertsemlidis, A. (2018). LMO1 functions as an oncogene by regulating TTK expression and correlates with neuroendocrine differentiation of lung cancer. Oncotarget, 9(51), pp. 29601–29618.
dc.identifier.doihttps://doi.org/10.18632/oncotarget.25642
dc.identifier.urihttps://hdl.handle.net/10877/8535
dc.language.isoen
dc.publisherImpact Journals LLC
dc.rights.licenseThis work is licensed under a Creative Commons Attribution 3.0 Unported License.
dc.sourceOncotarget, 2018, Vol. 9, No. 51, pp. 29601–29618.
dc.subjectlung cancer
dc.subjectneuroendocrine
dc.subjectTTK
dc.subjectLMO1
dc.subjectChemistry and Biochemistry
dc.titleLMO1 Functions as an Oncogene by Regulating TTK Expression and Correlates with Neuroendocrine Differentiation of Lung Cancer
dc.typeArticle

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