Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway

Wen, Gengyun; Li, Bingyan; Liao, Wupeng; Cheng, Simon K.; Hu, Burong; Calaf, Gloria M.; Lu, Ping; Tong, Jian; Hei, Tom K.

doi:10.3892/ijo.2011.1097

Cited by 18 publications

(19 citation statements)

References 39 publications

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“…These include high mobility group box 1 (HMGB1) and other cytokines, reactive oxygen species, and growth factors that promote sustained cell injury, inflammation, and DNA damage and stimulate cell growth, leading to fibrosis and/or carcinogenesis. 65 – 72 …”

Section: Environmental Exposurementioning

confidence: 99%

Consensus Report of the 2015 Weinman International Conference on Mesothelioma

Carbone

Kanodia

Chao

et al. 2016

Journal of Thoracic Oncology

129

155

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On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the Study of Lung Cancer, and the agenda was designed with significant input from staff at the U.S. National Cancer Institute and National Institute of Environmental Health Sciences. A multidisciplinary group of participants presented updates reflecting a range of disciplinary perspectives, including mineralogy, geology, epidemiology, toxicology, biochemistry, molecular biology, genetics, public health, and clinical oncology. The group identified knowledge gaps that are barriers to preventing and treating malignant mesothelioma (MM) and the required next steps to address barriers. This manuscript reports the group’s efforts and focus on strategies to limit risk to the population and reduce the incidence of MM. Four main topics were explored: genetic risk, environmental exposure, biomarkers, and clinical interventions. Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. MM is an almost entirely preventable malignancy as it is most often caused by exposure to commercial asbestos or mineral fibers with asbestos-like health effects, such as erionite. In the past in North America and in Europe, the most prominent source of exposure was related to occupation. Present regulations have reduced occupational exposure in these countries; however, some people continue to be exposed to previously installed asbestos in older construction and other settings. Moreover, an increasing number of people are being exposed in rural areas that contain noncommercial asbestos, erionite, and other mineral fibers in soil or rock (termed naturally occurring asbestos [NOA]) and are being developed. Public health authorities, scientists, residents, and other affected groups must work together in the areas where exposure to asbestos, including NOA, has been documented in the environment to mitigate or reduce this exposure. Although a blood biomarker validated to be effective for use in screening and identifying MM at an early stage in asbestos/ NOA-exposed populations is not currently available, novel biomarkers presented at the meeting, such as high mobility group box 1 and fibulin-3, are promising. There was general agreement that current treatment for MM, which is based on surgery and standard chemotherapy, has a modest effect on the overall survival (OS), which remains dismal. Additionally, although much needed novel therapeutic approaches for MM are being developed and explored in clinical trials, there is a critical need to invest in prevention research, in whic...

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Section: Environmental Exposurementioning

confidence: 99%

Consensus Report of the 2015 Weinman International Conference on Mesothelioma

Carbone

Kanodia

Chao

et al. 2016

Journal of Thoracic Oncology

129

155

View full text Add to dashboard Cite

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“…The C-terminal fragment of TGFBI induces human osteosarcoma and lung carcinoma cell apoptosis [ 23 , 24 ]. TGFBI knockdown promotes the proliferation of mesothelioma cells [ 25 ]. TGFBI evokes apoptosis of ovarian carcinoma cells [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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“…In some cases, overexpression of TGFBI in renal, pancreas or colon cancer cells induces cell migration and increases metastatic potential [22]. Others have shown that ectopic expression of TGFBI in transformed cells significantly suppresses tumorigenicity in multiple tumors, indicating that frequent downregulation of TGFBI is involved in tumor progression [21], [23]. Therefore, depending on the tissue, TGFBI functions as a promoter or suppressor of cancer growth [22].…”

Section: Introductionmentioning

confidence: 99%

Discoidin Domain Receptor 1 Contributes to Tumorigenesis through Modulation of TGFBI Expression

et al. 2014

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Discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family. The receptor is activated upon binding to its ligand, collagen, and plays a crucial role in many fundamental processes such as cell differentiation, adhesion, migration and invasion. Although DDR1 is expressed in many normal tissues, upregulated expression of DDR1 in a variety of human cancers such as lung, colon and brain cancers is known to be associated with poor prognosis. Using shRNA silencing, we assessed the oncogenic potential of DDR1. DDR1 knockdown impaired tumor cell proliferation and migration in vitro and tumor growth in vivo. Microarray analysis of tumor cells demonstrated upregulation of TGFBI expression upon DDR1 knockdown, which was subsequently confirmed at the protein level. TGFBI is a TGFβ-induced extracellular matrix protein secreted by the tumor cells and is known to act either as a tumor promoter or tumor suppressor, depending on the tumor environment. Here, we show that exogenous addition of recombinant TGFBI to BXPC3 tumor cells inhibited clonogenic growth and migration, thus recapitulating the phenotypic effect observed from DDR1 silencing. BXPC3 tumor xenografts demonstrated reduced growth with DDR1 knockdown, and the same xenograft tumors exhibited an increase in TGFBI expression level. Together, these data suggest that DDR1 expression level influences tumor growth in part via modulation of TGFBI expression. The reciprocal expression of DDR1 and TGFBI may help to elucidate the contribution of DDR1 in tumorigenesis and TGFBI may also be used as a biomarker for the therapeutic development of DDR1 specific inhibitors.

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Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway

Cited by 18 publications

References 39 publications

Consensus Report of the 2015 Weinman International Conference on Mesothelioma

Consensus Report of the 2015 Weinman International Conference on Mesothelioma

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

Discoidin Domain Receptor 1 Contributes to Tumorigenesis through Modulation of TGFBI Expression

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