The role of TGFBI (βig-H3) in gastrointestinal tract tumorigenesis

Abstract

BackgroundTGFβ-induced (TGFBI/βig-H3) is a protein inducible by TGFβ1 and secreted by many types of cells. It binds to collagen, forms part of the extracellular matrix (ECM), and interacts with integrins on cell surfaces. In this study, we investigated the role of TGFBI in tumorigenesis and the underlying mechanisms.MethodsPatient serum TGFBI levels were determined by ELISA. TGFBI transgenic and gene knockout mice and TGFBI-overexpressing liver cells were used for mechanistic studies.ResultsWe demonstrated that patients with cholangiocarcinomas, hepatic carcinomas or gastric carcinomas presented significantly elevated serum TGFBI levels, and the excess TGFBI was derived from the tumor masses. TGFBI overexpression in mice resulted in increased incidence of spontaneous tumors and N,N-diethylnitrosamine (DEN)-induced liver tumor nodules, compared to that in wild type (WT) mice, while TGFBI knockout mice were comparable to WT controls in these 2 aspects. TGFBI promoted the survival of Aml-12 liver cells with DNA damage after irradiation, and augmented their post-irradiation proliferation. It activated the FAK/AKT/AKT1S1/PRS6/EIF4EBP pathway, which is known to modulate cell survival and proliferation.ConclusionsOur data suggest that TGFBI functions as a promoter of certain gastrointestinal tract cancers. It provides a survival advantage to cells with DNA damage. Over a long time span, this advantage could translate into increased tumor risks.

Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma

“…IL1RN is an important anti-inflammatory regulator that acts as a dominant-negative interactor with IL1R1 to actively suppress immune activation. Another, highly enriched gene in immune cells within the tumor core was TGFBI (Figure 5C), a molecule with a yet unclear role in tumor formation (Han et al, 2015) that was previously thought to be expressed by neoplastic cells. TGFBI , which is induced by TGF-beta, is part of the non-Smad-mediated TGF-beta signaling pathway.…”

Assessment of Vitronectin, Soluble Epithelial-Cadherin and TGF-β1 as a Serum Biomarker with Predictive Value for Endometrial and Ovarian Cancers

“…36 In a similar manner, it was demonstrated that serum concentrations of TGF-β1 in gastric cancer patients were significantly higher than controls. 37 Han et al 23 were revealed that patients with cholangiocarcinomas, HCCs and gastric carcinomas presented increased serum TGF-β1 levels than non-cancer counterparts. It has been shown that the blockage of TGF-β causes upregulation of E-cadherin resulting in the reduction of migration and invasion of carcinoma cells 38 and then TGF-β1 expression negatively correlated with E-cadherin expression.…”

“…20,21 Increased TGF-β1 levels were reported in various cancers. 22,23 There are inadequate published data to verify the importance of serum VN, sE-cadherin and TGF-β1 concentrations in endometrial and ovarian cancers, up to now. Therefore, the investigation of changes in VN, sE-cadherin and TGF-β1 expressions and compare patients with healthy individuals was aimed for both diagnostic and protective purposes in these cancers.…”

High stromal transforming growth factor β–induced expression is a novel marker of progression and poor prognosis in gastric cancer

“…TGFBI was first described in a human lung adenocarcinoma cell line in 1992 as a protein that was inducible by transforming growth factor β (TGFβ), which was confirmed in various human cell types since its discovery . TGFBI was reported to play important roles in various clinical conditions such as malignancy, diabetes, and corneal dystrophy …”