Corona Armando, Blobe Gerard C
Department of Pharmacology and Cancer Biology, Duke University Medical center, USA.
Department of Pharmacology and Cancer Biology, Duke University Medical center, USA; Department of Medicine, Duke University Medical Center, USA.
Cell Signal. 2021 Aug;84:110028. doi: 10.1016/j.cellsig.2021.110028. Epub 2021 Apr 30.
The secreted extracellular protein, transforming growth factor beta induced (TGFBI or βIGH3), has roles in regulating numerous biological functions, including cell adhesion and bone formation, both during embryonic development and during the pathogenesis of human disease. TGFBI has been most studied in the context of hereditary corneal dystrophies, where mutations in TGFBI result in accumulation of TGFBI in the cornea. In cancer, early studies focused on TGFBI as a tumor suppressor, in part by promoting chemotherapy sensitivity. However, in established tumors, TGFBI largely has a role in promoting tumor progression, with elevated levels correlating to poorer clinical outcomes. As an important regulator of cancer progression, TGFBI expression and function is tightly regulated by numerous mechanisms including epigenetic silencing through promoter methylation and microRNAs. Mechanisms to target TGFBI have potential clinical utility in treating advanced cancers, while assessing TGFBI levels could be a biomarker for chemotherapy resistance and tumor progression.
分泌型细胞外蛋白转化生长因子β诱导蛋白（TGFBI或βIGH3）在调节多种生物学功能中发挥作用，包括胚胎发育期间以及人类疾病发病过程中的细胞黏附和骨形成。TGFBI在遗传性角膜营养不良方面研究最多，其中TGFBI的突变导致其在角膜中积累。在癌症研究中，早期研究将TGFBI视为肿瘤抑制因子，部分原因是它能提高化疗敏感性。然而，在已形成的肿瘤中，TGFBI在很大程度上促进肿瘤进展，其水平升高与较差的临床结果相关。作为癌症进展的重要调节因子，TGFBI的表达和功能受到多种机制的严格调控，包括通过启动子甲基化和微小RNA进行表观遗传沉默。靶向TGFBI的机制在治疗晚期癌症方面具有潜在的临床应用价值，而评估TGFBI水平可能是化疗耐药性和肿瘤进展的生物标志物。
