<scp>THBS</scp>1 is induced by <scp>TGFB</scp>1 in the cancer stroma and promotes invasion of oral squamous cell carcinoma

Pal, Samir Kumar; Nguyen, Chi Thi Kim; Morita, Keiichi; Miki, Yoshio; Kayamori, Kou; Yamaguchi, Akira; Sakamoto, Kei

doi:10.1111/jop.12430

Cited by 93 publications

(65 citation statements)

References 56 publications

(71 reference statements)

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“…Other studies have also reported that FAK/Src pathway was associated the OSCC cell migration [32, 33]. Moreover, Pal et al shows that thrombospondin-1 promotes migration of oral cancer cells and stimulates the expression of MMP-11 partly through the integrin signaling [34]. Therefore, we utilized a western blot to characterize the phosphorylation of FAK and Src in the MMP-11-overexpressed TW2.6 OSCC cells and showed that phosphorylation of FAK and Src was significantly increased.…”

Section: Discussionmentioning

confidence: 99%

MMP-11 promoted the oral cancer migration and FAK/Src activation

et al. 2017

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Matrix metalloproteinase-11 (MMP-11) has been observed in most invasive human carcinomas. The current study investigated the association between the clinicopathological characteristics and MMP-11 expression in oral squamous cell carcinoma (OSCC) patients. Immunohistochemistry (IHC) staining was performed to assess MMP-11 expression in 279 patients with OSCC. In addition, the metastatic effects of the MMP-11 overexpression on the OSCC cells were also investigated. We found that MMP-11 expression was present in 118/279 (42.3%) cases and expression of MMP-11 was associated with higher incidence of lymph node metastasis and worse grade of tumor differentiation. Importantly, OSCC patients with strong expression of MMP-11 had a significantly lower survival rate (p=0.010). Furthermore, MMP-11 overexpression in OSCC cells increased in vitro cell migration. Mechanistically, MMP-11 increased the cell motility of OSCC cells through focal adhesion kinase/Src kinase (FAK/Src) pathway. In conclusion, our results revealed that the MMP-11 expression in OSCC samples can predict the progression, especially lymph node metastasis, and the survival of OSCC patients in Taiwan.

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Section: Discussionmentioning

confidence: 99%

MMP-11 promoted the oral cancer migration and FAK/Src activation

et al. 2017

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“…The significant relationship between THBS1 and OC was detected using both RWR-based and SP-based methods. Several studies have indicated that THBS1 has crucial functions in oral tumorigenesis [72, 73]. THBS1 might be a potential diagnostic and therapeutic target for OC.…”

Section: Discussionmentioning

confidence: 99%

An integrated method for the identification of novel genes related to oral cancer

Lei¹,

Yang²,

Xing³

et al. 2017

PLoS ONE

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Cancer is a significant public health problem worldwide. Complete identification of genes related to one type of cancer facilitates earlier diagnosis and effective treatments. In this study, two widely used algorithms, the random walk with restart algorithm and the shortest path algorithm, were adopted to construct two parameterized computational methods, namely, an RWR-based method and an SP-based method; based on these methods, an integrated method was constructed for identifying novel disease genes. To validate the utility of the integrated method, data for oral cancer were used, on which the RWR-based and SP-based methods were trained, thereby building two optimal methods. The integrated method combining these optimal methods was further adopted to identify the novel genes of oral cancer. As a result, 85 novel genes were inferred, among which eleven genes (e.g., MYD88, FGFR2, NF-κBIA) were identified by both the RWR-based and SP-based methods, 70 genes (e.g., BMP4, IFNG, KITLG) were discovered only by the RWR-based method and four genes (L1R1, MCM6, NOG and CXCR3) were predicted only by the SP-based method. Extensive analyses indicate that several novel genes have strong associations with cancers, indicating the effectiveness of the integrated method for identifying disease genes.

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“…A paracrine interaction between tumor cells and CAFs lead to up‐regulation of MMP9, which is secreted and activated by OSCC tumor cells . A later study on OSCC found that thrombospondin (THBS) ‐1 released by fibroblasts further stimulated the production of MMP9 and other MMPs, supporting destruction of the ECM and cancer invasion . TGF‐β enhances MMP9 secretion and also triggers TAFs to secrete IL‐11, which may play a role in tumor progression and metastasis .…”

Section: Fibroblastsmentioning

confidence: 99%

“…Anti-IL-10 antibodies; TLR ligands and agonistic CD40 antibodies, anti-VEGF therapies, intratumoral injection of T. gondii; DC vaccines [24,30] Macrophages Anti-CCL2 antibodies; CSF1 and CSF1R antagonists; TLR ligand CpG and anti-IL-10 antibodies; IkK Kinase b inhibitors; HRG; FRb-targeted therapies; anti-CCL5 therapies; anti-CCL18 therapies; intravesicle installation of M. bovis; agonistic CD40 antibodies Anti-MARCO antibodies [39,44,49,[52][53][54][55][56][57][58][59] Pericytes VEGFR and PDGFR-b antagonists; VEGFR, PDGFR-b, and Tie-2 agonists; anti-RSG5 and anti-PD/PD-L1 therapies [61,68] Endothelial cells avb1, avb2, a5b1 integrin inhibitors; anti-VEGF and VEGFR agents [76,78] Fibroblasts Anti-CXCR-4 antibodies (SDF-1/CXCL12 inhibition); anti-VEGF-A antibodies and VEGF-R inhibitors; anti-PDGF-C/ PDGF-R inhibitors; MMP inhibitors; anti-IL6 antibodies; anti-HGF therapies; anti-FAP antibodies; Anti-TGFb and TGFbR inhibitors; anti-IL-11 therapies; anti-THSB1 therapies [80,86,90,[95][96][97][98] Neuronal cells NT3 and NT4 targeted therapies; GDNF inhibitors; anti-NGF antibodies; anti-PTN antibodies and N-syndecan inhibitors; BDNF inhibitors [99,105,109,111] Adipocytes Anti-IL-6 antibodies; anti-IL-8 antibodies; anti-CCL2 antibodies; anti-TIMP-1 antibodies; COX2 inhibitors, APN [119,120,122] APN, adiponectin; BDNF, brain-derived neurotrophic factor; CCL, chemokine ligand; CD, cluster of differentiation; COX, cyclooxygenase; CSF, colony stimulating factor; CSF1R, colony stimulating factor 1 receptor; CTLA, cytotoxic T-lymphocyteassociated protein; CXCL, C-X-C chemokine ligand; CXCR, C-X-C chemokine receptor; FAP, fibroblast activation protein; FRb, folate receptor beta; GDNF, glial cell line-derived neurotophic factor; HRG, histadine-rich glycoprotein; IL, interleukin; MMP, matrix metalloproteinase; NGF, n...…”

Section: Dendritic Cellsmentioning

confidence: 99%

Stromal contributions to the carcinogenic process

Spaw

Anant

Thomas

2016

Molecular Carcinogenesis

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Tumor-associated stromal cells are dynamic characters that endorse the carcinogenic process in a multitude of ways. The tumor microenvironment plays a crucial role throughout the tumor progression, which includes initiation, growth, invasion, and metastasis. The tumor microenvironment consists of cellular and non-cellular components. Tumor-associated stromal cell types include the microbiome, immune cells including macrophages, dendritic and T-cells, cells associated with blood and lymphatic vessels including pericytes and endothelial cells, fibroblasts, neuronal cells, and adipocytes. The non-cellular components of the microenvironment include matrix proteins and secreted factors. The development of therapies that target the mechanisms by which stromal cells contribute to successful tumorigenesis is major goal of upcoming cancer research. The purpose of this review is to present a comprehensive discussion of the role of each of the tumor-associated stromal cell types in the carcinogenic process with a special focus on target development and therapeutic intervention.

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THBS1 is induced by TGFB1 in the cancer stroma and promotes invasion of oral squamous cell carcinoma

Abstract: THBS1 is a tumor-specific ECM protein that is induced by TGFB1 and promotes migration of cancer cells and stimulates the expression of MMPs partly through the integrin signaling, thereby favoring OSCC invasion.

Cited by 93 publications

References 56 publications

MMP-11 promoted the oral cancer migration and FAK/Src activation

MMP-11 promoted the oral cancer migration and FAK/Src activation

An integrated method for the identification of novel genes related to oral cancer

Stromal contributions to the carcinogenic process

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