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.

Hmga2 collaborates with JAK2V617F in the development of myeloproliferative neoplasms

“…[51][52][53] Therefore, targets of Ezh2 other than Hmga2 may play a greater role in fibrosis in this context. RNA-seq also revealed that an Ezh2 deletion and overexpression of Hmga2 share deregulated oncogenic targets such as Lmo1 [54][55][56] in the presence of JAK2V617F. These observations give rise to the hypothesis that when the loss of Ezh2 and/or MIRlet-7 block the inhibition of some oncogenes, Hmga2 may synergistically accelerate such upregulation in the MPN stem cells.…”

LMO1 gene polymorphisms contribute to decreased neuroblastoma susceptibility in a Southern Chinese population

“…Apart from neuroblastoma, the LMO1 gene polymorphisms were also associated with acute lymphoblastic leukemia susceptibility [31]. Additionally, recent studies indicated that in the anti-EGFR therapy, overexpression of LMO1 may be a predictive marker for the colorectal cancer [32], lung cancer [33], and prostate cancer [34]. …”

Clinical significance of LMO1 in gastric cancer tissue and its association with apoptosis of cancer cells

“…LMO1 is one of the novel genes which has been reported in recent studies that is associated with a variety of malignancies such as leukemia, colorectal cancer and lung cancer in terms of tumor progression, metastasis and apoptosis ( 8 , 14 , 15 ). However, only a few studies focused on the relation between LMO1 and gastric cancer.…”