Overexpression of Betaig-h3 gene downregulates integrin α5β1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells

Zhao, Yongliang; Piao, Chang Q.; Hei, Tom K.

doi:10.1038/sj.bjc.6600304

Cited by 34 publications

(35 citation statements)

References 31 publications

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“…45,[55][56][57][58] Although tumorigenesis is determined by more factors than migration capacity and invasiveness only, our results of reduced migration upon BIGH3-expression in HSPCs are in line with e.g., the reduced BIGH3 expression in more tumorigenic bronchial cells.…”

Section: Discussionsupporting

confidence: 75%

BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells

Klamer

Kuijk

Hordijk

et al. 2013

Cell Adhesion & Migration

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Section: Discussionsupporting

confidence: 75%

BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells

Klamer

Kuijk

Hordijk

et al. 2013

Cell Adhesion & Migration

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“…Many of the biological effects of fibronectin are mediated via a5b1, which belongs to the integrin family of transmembrane receptors involved in cell-matrix interactions, cell-cell adhesion, differentiation, and wound healing (Akiyama et al, 1989;Loeser, 2002). This receptor has been shown to be expressed at low levels in BEAS-2B, in the human pulmonary epithelial cell line WI-26, and in human primary bronchial epithelial cells as determined by flow cytometry and RT-PCR analysis (Wang et al, 1996;Zhao et al, 2002). In our system, the effects of fibronectin on protein expression were mediated through a5b1, but not a2b1, suggesting a critical role for a5b1 in mediating the effects of fibronectin in these cells.…”

Section: Induction Of Cell Growth and Inhibition Of Apoptosis In Humamentioning

confidence: 70%

Fibronectin induces cell proliferation and inhibits apoptosis in human bronchial epithelial cells: pro-oncogenic effects mediated by PI3-kinase and NF-κB

2006

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The extracellular matrix glycoprotein, fibronectin, influences a variety of cellular functions including adhesion, migration, survival, differentiation, and growth. Fibronectin has also been shown to increase the migration and proliferation of human lung carcinoma cells. However, the role of fibronectin in controlling lung airway epithelial cell phenotype remains unknown. Here, we demonstrate that fibronectin stimulates the proliferation of human bronchial epithelial cells (BEAS-2B and 16-HBE). Of note, fibronectin induced the mRNA and protein expression of c-Myc and cyclin D1, while it decreased the expressions of cyclin-dependent kinase inhibitor p21WAF-1/CIP1/MDA-6 (p21) and the tumor suppressor gene phosphatase and tensin homolog deleted on chromosome ten (PTEN). Fibronectin also stimulated the phosphorylation of the phosphatidylinositol 3 kinase (PI3-K) downstream signal Akt. The inhibitor of PI3-K, Wortmannin, and anti-a5b1 integrin antibodies abrogated the effect of fibronectin on c-Myc, cyclin D1, p21, and PTEN expression. The stimulatory effect of fibronectin was mediated by nuclear factor kappaB (NF-jB) since fibronectin induced the expression of the p65 component of NF-jB and enhanced NF-jB DNA binding. Furthermore, we found that p65 small interfering RNA inhibited the effect of fibronectin on c-Myc, cyclin D1, p21, PTEN expression, and on fibronectin-induced cell proliferation. Finally, we found that fibronectin inhibits apoptosis by reducing DNA fragmentation and inhibiting the activities of caspases 3/7. Taken together, our findings demonstrate that fibronectin stimulates human bronchial epithelial cell growth and inhibits apoptosis through activation of NF-jB, which, in turn, increases the expression of c-Myc and cyclin D1 and decreases p21 and PTEN via a5b1 integrin-dependent signals that include PI3-K/Akt. Therefore, alternations in the extracellular matrix composition of the lung, with increased fibronectin, might promote epithelial cell growth and thereby contribute to oncogenesis in certain settings.

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“…The signal transduction pathway finder array (SuperArray, Frederick, MD), which includes 96 genes involved in 18 different signal transduction pathways, was used in the experiments. RNA from control, bystander, and irradiated cells were extracted by using TRIzol reagent (Invitrogen), and the same amount of total RNA was used for each array according the protocol provided by the manufacturer (26,27).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of radiation-induced bystander effect: Role of the cyclooxygenase-2 signaling pathway

Zhou

Ivanov

Gillespie

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

242

239

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The radiation-induced bystander effect is defined as ''the induction of biological effects in cells that are not directly traversed by a charged particle but are in close proximity to cells that are.'' Although these bystander effects have been demonstrated with a variety of biological endpoints in both human and rodent cell lines (as well as in 3D tissue samples), the mechanism of the phenomenon is not known. Although gap junction communication and the presence of soluble mediator(s) are both known to play important roles in the bystander response, the precise signaling molecules have yet to be identified. By using the Columbia University charged particle beam in conjunction with a strip dish design, we show here that the cyclooxygenase-2 (COX-2, also known as prostaglandin endoperoxide synthase-2) signaling cascade plays an essential role in the bystander process. Treatment of bystander cells with NS-398, which suppresses COX-2 activity, significantly reduced the bystander effect. Because the critical event of the COX-2 signaling is the activation of the mitogen-activated protein kinase pathways, our finding that inhibition of the extracellular signal-related kinase phosphorylation suppressed bystander response further confirmed the important role of mitogen-activated protein kinase signaling cascade in the bystander process. These results provide evidence that the COX-2-related pathway, which is essential in mediating cellular inflammatory response, is the critical signaling link for the bystander phenomenon.

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Overexpression of Betaig-h3 gene downregulates integrin α5β1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells

Cited by 34 publications

References 31 publications

BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells

BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells

Fibronectin induces cell proliferation and inhibits apoptosis in human bronchial epithelial cells: pro-oncogenic effects mediated by PI3-kinase and NF-κB

Mechanism of radiation-induced bystander effect: Role of the cyclooxygenase-2 signaling pathway

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