| ［1］ |
Shi Y， Massagué J. Mec hanisms of TGF-beta signaling from cell membrane to the nucleus［J］. Cell， 2003，113（6）：685-700.
|
| ［2］ |
Meulmeester E， Ten Dijke P. The dynamic roles of TGF-β in cancer ［J］. J Pathol， 2011，223（2）：205-218.
|
| ［3］ |
Massagué J. TGFbeta in Cancer ［J］. Cell， 2008，134（2）：215-230.
|
| ［4］ |
Massagué J， Seoane J， Wotton D. Smad transcription factors［J］. Genes Dev， 2005，19（23）：2783-2810.
|
| ［5］ |
Mu Y， Gudey SK， Landström M. Non-Smad signaling pathways［J］. Cell Tissue Res， 2012，347（1）：11-20.
|
| ［6］ |
Jang CW， Chen CH， Chen CC， et al. TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase［J］. Nat Cell Biol， 2002，4（1）：51-58.
|
| ［7］ |
Padua D， Massagué J. Roles of TGFbeta in metastasis ［J］. Cell Res， 2009，19（1）：89-102.
|
| ［8］ |
Suzuki HI， Kiyono K， Miyazono K. Regulation of autophagy by transforming growth factor-β （TGF-β） signaling ［J］. Autophagy，2010，6（5）：645-647.
|
| ［9］ |
Connolly EC， Freimuth J， Akhurst RJ. Complexities of TGF-β targeted cancer therapy［J］. Int J Biol Sci， 2012，8（7）：964-978.
|
| ［10］ |
Andarawewa KL， Kirshner J， Mott JD， et al. TGFβ： roles in DNA damage responses/ /Jakowlow SB. Transforming Growth Factor-β in Cancer Therapy， Volume Ⅱ ［M］. Clifton：Humana Press， 2008：321-333.
|
| ［11］ |
Bornstein S， White R， Malkoski S， et al. Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation ［J］. J Clin Invest， 2009，119（11）：3408-3419.
|
| ［12］ |
Derynck R， Akhurst RJ. Differentiation plasticity regulated by TGF-beta family proteins in development and disease ［J］. Nat Cell Biol， 2007，9（9）：1000-1004.
|
| ［13］ |
Wakefield LM， Roberts AB. TGF-beta signaling： positive and negative effects on tumorigenesis ［J］. Curr Opin Genet Dev，2002，12（1）：22-29.
|
| ［14］ |
Smith A， Teknos TN， Pan Q. Epithelial to mesenchymal transition in head and neck squamous cell carcinoma ［J］. Oral Oncol， 2013，49（4）：287-292.
|
| ［15］ |
Yang TL， Wu CT， Ko JY， et al. Significance of tumor satellite variables in reflecting the epithelial-mesenchymal transition of tongue cancer ［J］.Oral Oncol，2011，47（8）：720-724.
|
| ［16］ |
Sun L， Diamond ME， Ottaviano AJ， et al. Transforming growth factor-beta1 promotes matrix metalloproteinase-9-mediated oral cancer invasion through snail expression ［J］. Mol Cancer Res，2008，6（1）：10-20.
|
| ［17］ |
Qiao B， Johnson NW， Gao J. Epithelial-mesenchymal transition in oral squamous cell carcinoma triggered by transforming growth factor-β1 is Snail family-dependent and correlates with matrix metalloproteinase-2 and -9 expressions ［J］. Int J Oncol，2010，37（3）：663-668.
|
| ［18］ |
Orlichenko LS， Radisky DC. Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development［J］. Clin Exp Metastasis，2008，25（6）：593-600.
|
| ［19］ |
Joseph MJ， Dangi-Garimella S， Shields MA， et al. Slug is a downstream mediator of transforming growth factor-beta1-induced matrix metalloproteinase-9 expression and invasion of oral cancer cells ［J］. J Cell Biochem， 2009，108（3）：726-736.
|
| ［20］ |
Sinpitaksakul SN， Pimkhaokham A， Sanchavanakit N， et al.TGF-beta1 induced MMP-9 expression in HNSCC cell lines via Smad/MLCK pathway ［J］. Biochem Biophys Res Commun，2008，371（4）：713-718.
|
| ［21］ |
Cheng N，Chytil A，Shyr Y，et al.Transforming growth factor-beta signaling-deficient fibroblasts enhance hepatocyte growth factor signaling in mammary carcinoma cells to promote scattering and invasion ［J］. Mol Cancer Res， 2008，6（10）：1521-1533.
|
| ［22］ |
Daly AJ， McIlreavey L， Irwin CR. Regulation of HGF and SDF-1 expression by oral fibroblasts--implications for invasion of oral cancer ［J］. Oral Oncol， 2008，44（7）：646-651.
|
| ［23］ |
Dasgupta S， Bhattacharya-Chatterjee M， O'Malley BW Jr， et al. Inhibition of NK cell activity through TGF-beta1 by downregulation of NKG2D in a murine model of head and neck cancer ［J］. J Immunol，2005，175（8）：5541-5550.
|
| ［24］ |
Costa NL， Valadares MC， Souza PP， et al. Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma［J］. Oral Oncol， 2013，49（3）：216-223.
|
| ［25］ |
Lee JJ， Chang YL， Lai WL， et al. Increased prevalence of interleukin-17-producing CD4+ tumor infiltrating lymphocytes in human oral squamous cell carcinoma ［J］. Head Neck， 2011，33（9）：1301-1308.
|
| ［26］ |
Martinez GJ， Zhang Z， Reynolds JM， et al. Smad2 positively regulates the generation of Th17 cells ［J］. J Biol Chem， 2010，285（38）：29039-29043.
|
| ［27］ |
Schwarz S， Butz M， Morsczeck C， et al. Increased number of CD25 FoxP3 regulatory T cells in oral squamous cell carcinomas detected by chromogenic immunohistochemical double staining ［J］. J Oral Pathol Med， 2008，37（8）：485-489.
|
| ［28］ |
Strauss L，Bergmann C，Gooding W， et al. The frequency and suppressor function of CD4 + CD25highFoxp3+ T cells in the circulation of patients with squamous cell carcinoma of the head and neck ［J］. Clin Cancer Res， 2007，13（21）：6301-6311.
|
| ［29］ |
Costea DE， Hills A， Osman AH， et al. Identification of two distinctcarcinoma-associatedfibroblastsubtypeswith differential tumor-promoting abilities in oral squamous cell carcinoma ［J］. Cancer Res， 2013，73（13）：3888-3901.
|
| ［30］ |
Lu SL， Herrington H， Reh D， et al. Loss of transforming growth factor-beta type Ⅱ receptor promotes metastatic headand-neck squamous cell carcinoma ［J］. Genes Dev， 2006，20（10）：1331-1342.
|
| ［31］ |
Chu TH， Yang CC， Liu CJ， et al. miR-211 promotes the progression of head and neck carcinomas by targeting TGFβRⅡ［J］. Cancer Lett， 2013，337（1）：115-124.
|
| ［32］ |
Fukai Y， Fukuchi M， Masuda N， et al. Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma［J］. Int J Cancer， 2003，104（2）：161-166.
|
| ［33］ |
Guasch G， Schober M， Pasolli HA， et al. Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia ［J］. Cancer Cell， 2007，12（4）：313-327.
|
| ［34］ |
Kang SH， Bang YJ， Im YH， et al. Transcriptional repression of the transforming growth factor-beta type Ⅰreceptor gene by DNA methylation results in the development of TGF-beta resistance in human gastric cancer ［J］. Oncogene， 1999，18（51）：7280-7286.
|
| ［35］ |
Chen T， Yan W， Wells RG， et al. Novel inactivating mutations of transforming growth factor-beta typeⅠreceptor gene in headand-neck cancer metastases ［J］. Int J Cancer， 2001，93（5）：653-661.
|
| ［36］ |
Honjo Y， Bian Y， Kawakami K， et al. TGF-beta receptor Ⅰconditional knockout mice develop spontaneous squamous cell carcinoma ［J］. Cell Cycle， 2007，6（11）：1360-1366.
|
| ［37］ |
Bian Y， Terse A， Du J， et al. Progressive tumor formation in mice with conditional deletion of TGF-beta signaling in head and neck epithelia is associated with activation of the PI3K/Akt pathway［J］. Cancer Res， 2009，69（14）：5918-5926.
|
| ［38］ |
Iamaroon A， Pattamapun K， Piboonniyom SO. Aberrant expression of Smad4， a TGF-beta signaling molecule， in oral squamous cell carcinoma［J］. J Oral Sci， 2006，48（3）：105-109.
|
| ［39］ |
Takebayashi S， Ogawa T， Jung KY， et al. Identification of new minimally lost regions on 18q in head and neck squamous cell carcinoma［J］. Cancer Res， 2000，60（13）：3397-3403.
|
| ［40］ |
Xie W， Aisner S， Baredes S， et al. Alterations of Smad expression and activation in defining 2 subtypes of human head and neck squamous cell carcinoma. Head Neck， 2013，35（1）：76-85.
|
| ［41］ |
Qiu W， Schönleben F， Li X， et al. Disruption of transforming growth factor beta-Smad signaling pathway in head and neck squamous cell carcinoma as evidenced by mutations of SMAD2 and SMAD4 ［J］. Cancer Lett， 2007，245（1）：163-170.
|
| ［42］ |
Bornstein S， White R， Malkoski S， et al. Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation ［J］. J Clin Invest， 2009，119（11）：3408-3419.
|
| ［43］ |
Kutler DI， Auerbach AD， Satagopan J， et al. High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia［J］. Arch Otolaryngol Head Neck Surg， 2003，129（1）：106-112.
|
| ［44］ |
Wreesmann VB， Estilo C， Eisele DW， et al. Downregulation of Fanconi anemia genes in sporadic head and neck squamous cell carcinoma ［J］. ORL J Otorhinolaryn-gol Relat Spec， 2007，69（4）：218-225.
|
| ［45］ |
Berton TR，Matsumoto T，Page A，et al. Tumor formation in mice with condi-tional inactivation of Brca1 in epithelial tissues ［J］.Oncogene， 2003，22（35）：5415-5426.
|
| ［46］ |
Kitamura T， Kometani K， Hashida H， et al. SMAD4-deficient intestinal tumors recruit CCR1 + myeloid cells that promote invasion［J］. Nat Genet，2007，39（4）：467-475.
|
| ［47］ |
Kim BG， Li C， Qiao W， et al. Smad4 signalling in T cells is required for suppres-sion of gastrointestinal cancer ［J］. Nature，2006，441（7096）：1015-1019.
|
| ［48］ |
Malkoski SP， Wang XJ. Two sides of the story？ Smad4 loss in pancreatic cancer versus head and neck cancer ［J］. FEBS Lett， 2012，586（14）：1984-1992.
|
| ［49］ |
Li AG， Lu SL， Zhang MX， et al. Smad3 knockout mice exhibit a resistance to skin chemical carcinogenesis ［J］. Cancer Res， 2004，64（21）：7836-7845.
|
| ［50］ |
Hoot KE， Lighthall J， Han G， et al. Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression ［J］. J Clin Invest，2008，118（8）：2722-2732.
|
| ［51］ |
Hoot KE， Oka M， Han G， et al. HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion ［J］. J Clin Invest， 2010，120（10）：3606-3616.
|