Biomedical subjects

Wenjun Guo

Publications and source records attributed to Wenjun Guo.

6 recordsLinked to original sources

PubMed2006

Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis.

Amplification of the ErbB2 locus, which encodes a receptor tyrosine kinase, is common in aggressive breast tumors and correlates with poor prognosis. The mechanisms underlying ErbB2-mediated breast carcinoma progression remain incompletely defined. To examine the role of the signaling and cell-adhesion receptor beta 4 integrin during ErbB2-mediated tumorigenesis, we introduced a targeted deletion of the beta 4 signaling domain into a mouse model of ErbB2-induced mammary carcinoma. Loss of beta 4 signaling suppresses mammary tumor onset and invasive growth. Ex vivo studies indicate that beta 4 forms a complex with ErbB2 and enhances activation of the transcription factors STAT3 and c-Jun. STAT3 contributes to disruption of epithelial adhesion and polarity, while c-Jun is required for hyperproliferation. Finally, deletion of the beta 4 signaling domain enhances the efficacy of ErbB2-targeted therapy. These results indicate that beta 4 integrin promotes tumor progression by amplifying ErbB2 signaling and identify beta 4 as a potential target for molecular therapy of breast cancer.

Animals↗

PubMed2006

Synthesis and two-dimensional correlation infrared spectroscopy study of an organic-inorganic hybrid compound constructed by [Mo(5)P(2)O(23)] and Cu-imidazole components.

A novel compound, (Himi)(H(3)O) [Cu(imi)(2)](2)[P(2)Mo(5)O(23)].H(2)O 1 (imi=imidazole), was synthesized by hydrothermal method and characterized by X-ray single analysis, ESR spectrum, one-dimensional (1D) infrared spectroscopy and two-dimensional (2D) correlation infrared spectroscopy under thermal and magnetism perturbation. Crystal data for the compound 1: orthorhombic system, space group Pnma, a = 14.580(3)A, b = 21.073(4)A, c = 16.664(3)A, Z = 4. It consists of the Mo-Cu building-blocks [Cu(imi)(4)](2)[P(2)Mo(5)O(23)](2-), protonated imidazole cations and water molecules. In the Mo-Cu building-blocks, [Mo(5)P(2)O(23)](6-) clusters are linked by {Cu(imi)(4)}(2+) group to form a two-dimension parallelogram griddling structure. From the 2D IR correlation spectroscopy analyses, it is discovered that the intensity changes of Mo=O and P-O band are sensitive to the temperature variation, whereas the Mo-O bond linking to Cu(2+) can be remarkably affected by the magnetism variation. Furthermore, the intensity changes of P-O bands occur prior to that of the Mo=O band during the temperature elevation.

Chemistry, Inorganic↗

PubMed2005

p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors from the bone marrow.

Neoangiogenesis involves both bone marrow-derived myelomonocytic and endothelial progenitor cells as well as endothelial cells coopted from surrounding vessels. Cytokines induce these cells to proliferate, migrate, and exit the cell cycle to establish the vasculature; however, which cell cycle regulators play a role in these processes is largely unknown. Here, we report that mice lacking the cell cycle inhibitors p130 and p27 show defects in tumor neoangiogenesis, both in xenografts and spontaneously arising tumors. This defect is associated with impaired mobilization of endothelial and myelomonocytic angiogenic progenitors from the bone marrow. This article documents the role of these molecules in angiogenesis and further suggests that cell expansion and mobilization from the bone marrow of angiogenic precursors are separable events.

Animals↗

PubMed2005

Targeted deletion of the integrin beta4 signaling domain suppresses laminin-5-dependent nuclear entry of mitogen-activated protein kinases and NF-kappaB, causing defects in epidermal growth and migration.

The alpha6beta4 integrin-a laminin-5 receptor-mediates assembly of hemidesmosomes and recruitment of Shc and phosphoinositide 3-kinase through the unique cytoplasmic extension of beta4. Mice carrying a targeted deletion of the signaling domain of beta4 develop normally and do not display signs of skin fragility. The epidermis of these mice contains well-structured hemidesmosomes and adheres stably to the basement membrane. However, it is hypoplastic due to reduced proliferation of basal keratinocytes and undergoes wound repair at a reduced rate. Keratinocytes from beta4 mutant mice undergo extensive spreading but fail to proliferate and migrate in response to epidermal growth factor (EGF) on laminin-5. EGF causes significant phosphorylation of extracellular signal-regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) and phosphorylation and degradation of IkappaB in beta4 mutant cells adhering to laminin-5. Unexpectedly, however, ERK, JNK, and NF-kappaB remain in the cytoplasm in beta4 mutant cells on laminin-5, whereas they enter effectively into the nucleus in the same cells on fibronectin or in wild-type cells on both matrix proteins. Inhibitor studies indicate that alpha6beta4 promotes keratinocyte proliferation and migration through its effect on NF-kappaB and P-JNK. These findings provide evidence that beta4 signaling promotes epidermal growth and wound healing through a previously unrecognized effect on nuclear translocation of NF-kappaB and mitogen-activated protein kinases.

Active Transport, Cell Nucleus↗

PubMed2004

Integrin beta4 signaling promotes tumor angiogenesis.

Mice carrying a targeted deletion of the signaling portion of the integrin beta4 subunit display drastically reduced angiogenesis in response to bFGF in the Matrigel plug assay and to hypoxia in the retinal neovascularization model. Molecular cytology indicates that alpha6beta4 signaling promotes branching of beta4+ medium- and small-size vessels into beta4- microvessels without exerting a direct effect on endothelial cell proliferation or survival. Signaling studies reveal that alpha6beta4 signaling induces endothelial cell migration and invasion by promoting nuclear translocation of P-ERK and NF-kappaB. Upon subcutaneous implantation of various cancer cells, the mutant mice develop smaller and significantly less vascularized tumors than wild-type controls. These results provide genetic evidence that alpha6beta4 signaling promotes the onset of the invasive phase of pathological angiogenesis and hence identify a novel target for antiangiogenic therapy.

Animals↗

PubMed2004

Integrin signalling during tumour progression.

During progression from tumour growth to metastasis, specific integrin signals enable cancer cells to detach from neighbouring cells, re-orientate their polarity during migration, and survive and proliferate in foreign microenvironments. There is increasing evidence that certain integrins associate with receptor tyrosine kinases (RTKs) to activate signalling pathways that are necessary for tumour invasion and metastasis. The effect of these integrins might be especially important in cancer cells that have activating mutations, or amplifications, of the genes that encode these RTKs.

Cell Movement↗