Abstract
The members of the family of epithelial membrane proteins (EMPs), EMP1, EMP2, and EMP3, possess four putative transmembrane domain structures and are composed of approximately 160 amino acid residues. EMPs are encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family. The GAS3/PMP22 family members play roles in cell migration, growth, and differentiation. Evidence indicates an association of these molecules with cancer progression and metastasis. Each EMP has pro- and anti-metastatic functions that are likely involved in the complex mechanisms of cancer progression. We have recently demonstrated that the upregulation of EMP1 expression facilitates cancer cell migration and invasion through the activation of a small GTPase, Rac1. The inoculation of prostate cancer cells overexpressing EMP1 into nude mice leads to metastasis to the lymph nodes and lungs, indicating that EMP1 contributes to metastasis. Pro-metastatic properties of EMP2 and EMP3 have also been proposed. Thus, targeting EMPs may provide new insights into their clinical utility. Here, we highlight the important aspects of EMPs in cancer biology, particularly invasiveness and metastasis, and describe recent therapeutic approaches.
Highlights
Cancer metastasis describes the lethal process of the journey of cancer cells from the original site of tumor formation to other major organs, such as the kidney, liver, and lung [1,2]
EMP1 contributes to the metastasis of glioblastoma multiforme (GBM)
We have recently found that EMP1 enhances the progression of prostate cancer in vitro and in vivo, and that the mRNA and protein levels of EMP1 are upregulated in co-cultures of human prostate cancer and stromal cells [22]
Summary
Cancer metastasis describes the lethal process of the journey of cancer cells from the original site of tumor formation to other major organs, such as the kidney, liver, and lung [1,2]. In an animal protein 1 (EMP1), is upregulated in co-cultures of human prostate cancer cells and prostate stromal model, EMP1 significantly enhances the migration of cancer cells and the formation of metastatic cells [22] This co-culture system was utilized to mimic a tumor microenvironment. Increased EMP1 expression in patients with prostate model, EMP1 significantly enhances theis migration of cancer cells and the formation of metastatic cancer occurs at the invasive front and associated with malignancy. In this context, we highlight in lesions in the lymph nodes, lungs, or both. In the last part of this review, we consider future therapeutic approaches to improve the prognosis of cancers according
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