Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) identifies a specific lung disorder characterized by chronic, progressive fibrosing interstitial pneumonia of unknown etiology, which lacks effective treatment. According to the current pathogenic perspective, the aberrant proliferative events in IPF resemble those occurring during malignant transformation.Main bodyReceptor tyrosine kinases (RTK) are known to be key players in cancer onset and progression. It has been demonstrated that RTK expression is sometimes also altered and even druggable in IPF. One example of an RTK—the MET proto-oncogene—is a key regulator of invasive growth. This physiological genetic program supports embryonic development and post-natal organ regeneration, as well as cooperating in the evolution of cancer metastasis when aberrantly activated. Growing evidence sustains that MET activation may collaborate in maintaining tissue plasticity and the regenerative potential that characterizes IPF.ConclusionThe present work aims to elucidate—by applying the logic of simplicity—the bio-molecular mechanisms involved in MET activation in IPF. This clarification is crucial to accurately design MET blockade strategies within a fully personalized approach to IPF.
Highlights
Idiopathic pulmonary fibrosis (IPF) identifies a specific lung disorder characterized by chronic, progressive fibrosing interstitial pneumonia of unknown etiology, which lacks effective treatment
MET proto-oncogene is a Receptor tyrosine kinases (RTK) that is a key regulator of invasive growth [7], which is the biological program that orchestrates dynamic changes in tissues leading to cell proliferation, survival and migration across the extracellular matrix (ECM) and which can be inappropriately overexpressed in cancer spreading and metastatization
Scatter factors (HGF and Macrophage-stimulating Protein-MSP) belong to the plasminogen family of proteins, which is defined by the presence of at least one characteristic domain known as the kringle domain; a serine-protease domain and an activation segment that is located between the kringle and the protease domains
Summary
The molecular pathways involved in the metastatic process in cancer are shared with IPF. MET expression in myofibroblasts behaves as in cancer stem cells, where it sustains the inherent self-renewing, self-preserving and invasive growth phenotype [8, 19]. These notions indicate three clinical implications: (1) MET is a versatile candidate for targeted therapeutic intervention in IPF. Investigational Clinical Oncology (INCO), IRCCS Candiolo Cancer Institute-FPO, Candiolo, 20060 Turin, Italy. Experimental Clinical Molecular Oncology (ECMO), IRCCS Candiolo Cancer Institute-FPO, Candiolo, 20060 Turin, Italy Author details 1 Pneumology Unit, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, Piazzale Golgi 19, 27100 Pavia, Italy. 2 Investigational Clinical Oncology (INCO), IRCCS Candiolo Cancer Institute-FPO, Candiolo, 20060 Turin, Italy. 3 Experimental Clinical Molecular Oncology (ECMO), IRCCS Candiolo Cancer Institute-FPO, Candiolo, 20060 Turin, Italy
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