EMMPRIN regulates the canonical Wnt/beta-catenin signaling pathway, a potential role in accelerating lung tumorigenesis.
Advances in the field of tumor biology have identified that tumor cells co-opt developmental signaling pathways of embryonic stem cells and thus gain the ability to proliferate, differentiate and alter cell-cell interactions. One such pathway is the Wnt/beta-catenin signaling pathway. High levels of EMMPRIN expression have been shown to correlate with poor prognosis and metastasis in a broad range of tumors. Although a variety of functions are attributed to EMMPRIN in tumorigenesis, the specific mechanism(s) through which it can exert its effects have not been elucidated, until now. In this study, we identify EMMPRIN as a novel regulator of the canonical Wnt/beta-catenin signaling pathway in lung cancer. Increasing EMMPRIN expression levels in lung cancer epithelial cells upregulated the beta-catenin signaling pathway and silencing EMMPRIN inhibited beta-catenin signaling, cell migration, proliferation, anchorage-independent growth and tumor growth in a mouse tumor xenograft model. These results provide a compelling rationale for targeting EMMPRIN for anticancer therapies. Understanding the molecular mechanisms driving EMMPRIN-induced lung tumorigenesis will provide enormous benefits in developing new therapeutic treatments for this and other forms of cancer.
Sidhu
S S
SS
Divisions of Pulmonary and Critical Care and Allergy/Immunology, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA. ssidhu@ucsf.edu
Nawroth
R
R
Retz
M
M
Lemjabbar-Alaoui
H
H
Dasari
V
V
Basbaum
C
C
D000818:Animals; D017209:Apoptosis; D051926:Basigin / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
C497886:BSG protein, human; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; D051926:Basigin; D020782:Matrix Metalloproteinases