title: LMO1 is a novel oncogene in lung cancer, and its overexpression is a new predictive marker for anti-EGFR therapy.
abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality in the world. We report that one oncogene amplified on chromosome 3q26, LMO1, a master transcriptional regulator of stemness, operates to drive strong growth phenotype in NSCLC. We first validate gene expression changes of LMO genes by real-time quantitative RT-PCR real-time quantitative reverse transcriptase-polymerase chain reaction analysis and immunohistochemistry, and we identified gene overexpression of LMO1 compared with non-cancerous tissues (p < 0.01). Next, we discovered that LMO1 promoted cancer cell proliferation in our in vitro/vivo cell proliferation assay, and our cell signaling experiments showed that LMO1 expression correlated with elevated AKT phosphorylation in NSCLC, while the AKT phosphorylation was required for LMO1's oncogenic effects. In addition, we compared complete response rate, stable disease rate, disease progression rate, and the disease control rate of patient with different LMO1 gene expression which pointed to the usefulness of LMO1 overexpression, as a new predictive marker for responsiveness to cetuximab. All in all, LMO1 is a commonly activated tumor promoter that activates AKT signaling in NSCLC and a new predictive marker for targeted therapy.
authors.affiliation: Department of TCM, Jilin Province Tumor Hospital, Changchun, 130012, Jilin Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jili
authors.initials: J
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Guo
authors.forename: Niancai
authors.initials: N
authors.lastname: Jing
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000068818:Cetuximab; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009857:Oncogenes; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C065072:LMO1 protein, human; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D000068818:Cetuximab