Abstract
Metastatic spread of cancer is a leading cause for the loss of life from this disease. In metastatic cascade, cells undergo multifaceted phenotypic transformations that include breakdown of extracellular matrix (ECM) encasing the tumor, cancer cell migration and invasion of surrounding tissues, and relocation of cancer cells in secondary organs. Recently a multitasking protein, A Disintegrin and Metalloprotease-12 (ADAM-12), has attracted particular interest because of its potential roles in tumor growth and development by facilitating remodeling of extracellular matrix and cell migration that are so essential for cancer growth and metastasis. ADAM-12 is an active metalloproteinase; it regulates release of growth factors and is capable of promoting cell–cell and cell–matrix adhesion and cell signaling as well. Overexpression of ADAM-12 is reported in many types of human cancers. Furthermore, a statistical correlation between the urinary levels of ADAM-12 in breast and bladder cancer patients and cancer progression has been found. These results suggested that ADAM-12 could be used as a diagnostic marker. In addition to cancers, increase of ADAM-12 expression is linked to the pathogenesis of osteoarthritis, cardiac hypertrophy, and Alzheimer’s disease, as well as during high-fat diet-induced obesity. This review is meant to provide a broad overview of the regulatory pathways by which ADAM-12 could be expressed to contribute towards tumor development, accelerate tumor progression, and metastasis. A better understanding of the regulation of this multifunctional protein that could well be used as a new therapeutic option.
Published Version
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