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.
Highlights
Breast cancer is one of the most debilitating human carcinomas and has the second highest mortality rate after lung cancer in women [1]
It is known that most breast carcinomas occur as a result of alterations in oncogenes and tumor suppressor genes, which regulate the signal transduction pathways involved in cell proliferation, differentiation and apoptosis
Aberrant expression of Nemo-like kinase (NLK) was correlated with proliferation and apoptosis in hepatocellular carcinoma [3], prostate cancer
Summary
Breast cancer is one of the most debilitating human carcinomas and has the second highest mortality rate after lung cancer in women [1]. There is a very large body of information on the development and progression of breast cancer, all key factors have not yet been elucidated. Wnt proteins belong to a large family of secreted signaling molecules that direct cell growth and fate [2]. Several lines of recent evidence show that the Wnt pathway is critical for the development of a normal mammary gland, whereas aberrant Wnt signaling is observed in cancer [1]. The Nemo-like kinase (NLK) of the Wnt signaling pathway is a member of the extracellular-signal regulated kinase/microtubule-associated protein kinase MAPK) and cyclin-dependent kinase (Cdk) families [3]. NLK functions downstream of transforming growth factor b-activated kinase (TAK1), which is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK or MAP3K) family [4]
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