LTBP4 in Health and Disease

Latent transforming growth factor ꞵ (TGFꞵ)-binding protein (LTBP) 4, a member of the LTBP family, shows structural homology with fibrillins. Both these protein types are characterized by calcium-binding epidermal growth factor-like repeats interspersed with 8-cysteine domains. Based on its domain composition and distribution, LTBP4 is thought to adopt an extended structure, facilitating the linear deposition of tropoelastin onto microfibrils. In humans, mutations in LTBP4 result in autosomal recessive cutis laxa type 1C, characterized by redundant skin, pulmonary emphysema, and valvular heart disease. LTBP4 is an essential regulator of TGFꞵ signaling and is related to development, immunity, injury repair, and diseases, playing a central role in regulating inflammation, fibrosis, and cancer progression. In this review, we focus on medical disorders or diseases that may be manipulated by LTBP4 in order to enhance the understanding of this protein.

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Transforming growth factor-β-induced epithelial–mesenchymal transition facilitates epidermal growth factor-dependent breast cancer progression

Oncogene ◽

10.1038/onc.2010.377 ◽

2010 ◽

Vol 29 (49) ◽

pp. 6485-6498 ◽

Cited By ~ 139

Author(s):

M K Wendt ◽

J A Smith ◽

W P Schiemann

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cancer Progression ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Transforming Growth Factor Β ◽

Breast Cancer Progression ◽

Mesenchymal Transition ◽

Epidermal Growth

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Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions

International Journal of Molecular Sciences ◽

10.3390/ijms19092787 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2787 ◽

Cited By ~ 12

Author(s):

Takeshi Tsuda

Keyword(s):

Growth Factor ◽

Cancer Progression ◽

Calcium Binding ◽

Structural Integrity ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Elastic Fibers ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Pathological Conditions

Transforming growth factor (TGF)-β is a multifunctional peptide growth factor that has a vital role in the regulation of cell growth, differentiation, inflammation, and repair in a variety of tissues, and its dysregulation mediates a number of pathological conditions including fibrotic disorders, chronic inflammation, cardiovascular diseases, and cancer progression. Regulation of TGF-β signaling is multifold, but one critical site of regulation is via interaction with certain extracellular matrix (ECM) microenvironments, as TGF-β is primarily secreted as a biologically inactive form sequestrated into ECM. Several ECM proteins are known to modulate TGF-β signaling via cell–matrix interactions, including thrombospondins, SPARC (Secreted Protein Acidic and Rich in Cystein), tenascins, osteopontin, periostin, and fibulins. Fibulin family members consist of eight ECM glycoproteins characterized by a tandem array of calcium-binding epidermal growth factor-like modules and a common C-terminal domain. Fibulins not only participate in structural integrity of basement membrane and elastic fibers, but also serve as mediators for cellular processes and tissue remodeling as they are highly upregulated during embryonic development and certain disease processes, especially at the sites of epithelial–mesenchymal transition (EMT). Emerging studies have indicated a close relationship between fibulins and TGF-β signaling, but each fibulin plays a different role in a context-dependent manner. In this review, regulatory interactions between fibulins and TGF-β signaling are discussed. Understanding biological roles of fibulins in TGF-β regulation may introduce new insights into the pathogenesis of some human diseases.

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