Nemo-Like Kinase Associated with Proliferation and Apoptosis by c-Myb Degradation in Breast Cancer

Abstract

Nemo-like kinase (NLK), a mediator of the Wnt signaling pathway, binds directly to c-Myb, leading to its phosphorylation, ubiquitination and proteasome-dependent degradation. NLK was significantly downregulated in the breast cancer tissues compared to corresponding normal tissues. NLK expression was negatively correlated with c-Myb expression. NLK suppressed proliferation, induced apoptosis and mediated c-Myb degradation in MCF-7 cells via a mechanism that seems to involve c-myc and Bcl2. These findings might provide a novel target for therapeutic intervention in patients with breast cancer.

Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma

“…Furthermore, NLK was significantly downregulated in the breast cancer tissues and negatively correlated with c-Myb expression. NLK suppressed cell proliferation, induced apoptosis, and regulated c-Myb degradation in MCF-7 breast cancer cell Line via c-myc and Bcl2 [21]. NLK was also lowly expressed in NSCLC and significantly associated with NSCLC histological grade, clinical stage, lymph node status, and Ki-67 [5].…”

The emerging role of Nemo-like kinase (NLK) in the regulation of cancers

“…It has been known that NLK phosphorylates c-Myb at multiple sites resulting in its ubiquitination and proteasome-dependent degradation [43]. NLK-induced degradation of c-Myb is associated with proliferation and apoptosis in MCF-7 cells [14] (Fig. 2).…”

“…In glioblastoma cell U87MG, upregulated NLK reduces numbers of cells but increases cell apoptosis [17]. Overexpression of NLK prevents proliferation and elicits apoptosis in breast cancer cell MCF-7 [14]. Therefore, based on the evidences given before, upregulation of NLK might be of important therapeutic application in the treatment of these cancers.…”

“…In ovarian cancer, NLK is predominant in the nucleus that is downregulated compared to normal human ovarian tissues, and patients with low NLK expression have poorer outcome than those with NLK overexpression [13]. NLK is mainly expressed in the nuclei and is significantly downregulated in the breast cancer tissues compared to corresponding normal tissues [14,15]. The staining intensity of NLK is higher in breast benign tumor tissues than in carcinoma specimens, which may contribute to the progression of breast carcinoma [14].…”

“…NLK is mainly expressed in the nuclei and is significantly downregulated in the breast cancer tissues compared to corresponding normal tissues [14,15]. The staining intensity of NLK is higher in breast benign tumor tissues than in carcinoma specimens, which may contribute to the progression of breast carcinoma [14]. Compared with the non-tumorous adjacent ones, NLK protein level is dramatically decreased in the non-small-cell lung cancer (NSCLC) tissues.…”