研究领域
细胞对外界刺激的反应不仅取决于细胞本身特性,同时也受到细胞微环境(microenvironment)的调节。以上皮细胞为例,其细胞微环境包括细胞外基质(Extracellular Matrix, ECM),生长因子/激素,蛋白酶等活性分子以及成纤维细胞,微血管,免疫系统等其它细胞形态。细胞微环境的组成也处于动态的平衡当中。细胞与细胞微环境的相互作用在组织发育以及疾病发生过程当中起到至关重要的作用。本课题组将主要以乳腺癌作为模型,利用生物化学,细胞生物学的手段以及小鼠模型研究在肿瘤发生及转移过程中癌症细胞与细胞微环境的相互作用,并着重研究:
1) 癌细胞对细胞微环境的调节。特别是成纤维细胞向癌症耦联成纤维细胞/活性成纤维细胞(cancer-associated fibroblasts, CAFs;reactive fibroblasts)的转化。
2) 癌症耦联的细胞微环境诱导上皮细胞的恶性转化。
3) 癌细胞对细胞微环境的入侵及肿瘤的转移
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Zhang R#, Gao Y#, Zhao X#, Gao M#, Wu Y, Han Y, Qiao Y, Luo Z, Yang L, Chen J, and Ge G*. (2018) FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis. PLOS Biol. 16(8): e2001493
Wang S, Wu C, Zhang Y, Zhong Q, Sun H, Cao W, Ge G, Li G*, Zhang XF*, and Chen J*. (2018) Integrin α4β7 switches its ligand specificity via distinct conformer-specific activation.J Cell Biol. [Epub ahead of print]
Zhang R#, Ma H#, Gao Y#, Wu Y, Qiao Y, Geng A, Cai C, Han Y, Zeng YA, Liu X*, and Ge G*. (2018) Th-POK regulates mammary gland lactation through mTOR-SREBP pathway. PLoS Genet. 14(2):e1007211. doi:10.1371/journal.pgen.1007211.
Gao Y, Wu Y, Han Y, and Ge G*. (2017) Extracellular Matrix and Cancer-associated Fibroblasts. Progr Biochem Biophy. 44(8): 660~671
Huang G, Ge G, Izzi V, and Greenspan DS*. (2017) a3(V) collagen regulates breast tumor growth via glypican-1. Nat Commun. 8:14351. doi: 10.1038/ncomms14351.
Xiao Q, Jiang Y, Liu Q, Yue J, Liu C, Zhao X, Qiao Y, Ji H, Chen J and Ge G*. (2015) Minor type IV collagen a5 chain promotes cancer progression through discoidin domain receptor-1. PLOS Genet, 11(5): e1005249. doi:10.1371/journal.pgen.1005249
Xia P, Zhang R and Ge G*. (2015) C/EBPβ mediates TNF-α-induced cancer cell migration by inducing MMP expression dependent on p38 MAPK. J Cell Biochem, 116(12):2766-77.
Chen C#, Wang X#, Xiong X#, Liu Q, Huang Y, Xu W, Hu J, Ge G, Ling K*. (2015) Targeting Type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis. Oncogene. 34(35):4635-46.
Cheng T#, Liu Q#, Zhang R, Zhang Y, Chen J, Yu R, and Ge G*. (2014) Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation. J Mol Cell Biol. 6(6):506-15.
Jiang Y#, Zhao X#, Xiao Q, Liu Q, Ding K, Yu F, Zhang R, Zhu T, and Ge G*. (2014) Snail and Slug mediate tamoxifen resistance in breast cancer cells through activation of EGFR-ERK independent of epithelial-mesenchymal transition. J Mol Cell Biol. 6, 352-4.
Han X#, Li F#, Fang Z, Gao Y, Li F, Fang R, Yao S, Sun Y, Li L, Zhang W, Ma H, Xiao Q, Ge G, Fang J, Wang H, Zhang L, Wong KK, Chen H, Hou Y, Ji H*. (2014) Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma. Nat Commun. 5, 3261
Xiao Q, and Ge G*. (2012) Lysyl Oxidase, Extracellular Matrix Remodeling and Cancer Metastasis. Cancer Microenviron. 5, 261-73
Xiao G, Deng A, Liu H, Ge G, and Liu, X*. (2012) Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1. Proc Natl Acad Sci U S A. 109, 15419-24
Ma HM, and Ge G*. (2012) Desmoplasia and cancer. Chin J Cell Biol. 34(7): 635-44.
Sun H, Wu Y, Qi J, Pan Y, Ge G, and Chen J*. (2011) The CC' and DE loops in Ig domains 1 and 2 of MAdCAM-1 play different roles in MAdCAM-1 binding to low- and high-affinity integrin a4b7. J Biol Chem. 286, 12086-12092
Gao Y, Ge G*, Ji H*.(2011) LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor suppressor. Protein Cell. 2, 99-107
Huang G#, Ge G#, Wang D#, Gopalakrishnan B, Butz DH, Colman RJ, Nagy A, Greenspan DS*. (2011) α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues. J Clin Invest. 121, 769-783
Gao Y#, Xiao Q#, Ma H#, Li L, Liu J, Feng Y, Fang Z, Wu J, Han X, Zhang J, Sun Y, Wu G, Padera R, Chen H, Wong KK, Ge G*, Ji H*. (2010) LKB1 inhibits lung cancer progression through lysyl oxidase and extracellular matrix remodeling. Proc Natl Acad Sci U S A. 107:18892-7
Huang G#, Zhang Y#, Kim B, Ge G, Annis DS, Mosher DF, Greenspan DS*. (2009) Fibronectin binds and enhances the activity of bone morphogenetic protein 1. J Biol Chem. 284(38):25879-88
Kobayashi K#, Luo M#, Zhang Y#, Wilkes DC, Ge G, Grieskamp T, Yamada C, Liu TC, Huang G, Basson CT, Kispert A, Greenspan DS*, Sato TN*. (2009) Secreted Frizzled-related protein 2 is a procollagen C proteinase enhancer with a role in fibrosis associated with myocardial infarction. Nat Cell Biol. 11(1):46-55.