LMO1 is a novel oncogene in colorectal cancer and its overexpression is a new predictive marker for anti-EGFR therapy.
Colorectal cancer (CRC) is the third 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 CRC. The gene expression changes of LMO1 in human CRC tissues compared with noncancerous tissues were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of LMO1 in CRC. Moreover, we discovered that LMO1 promoted cancer cell proliferation in vitro/in vivo and LMO1 expression correlated with elevated AKT phosphorylation in CRC while the AKT phosphorylation was required for oncogenic effects of LMO1. Next, our data point 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 CRC and a new predictive marker for targeted therapy.
Department of General Surgery, Wendeng Central Hospital, Wendeng, Shandong Province, 264400, China.
Junguang
J
Liu
Peiyun
P
Yan
Niancai
N
Jing
Jili
J
Yang
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015415:Biomarkers; D049109:Cell Proliferation; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009857:Oncogenes; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000068818:Cetuximab; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D060588:LIM Domain Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C065072:LMO1 protein, human; C508053:ERBB2 protein, human