Metadherin regulates metastasis of squamous cell carcinoma of the head and neck via AKT signalling pathway-mediated epithelial–mesenchymal transition

Yu, Changyun; Liu, Yong; Tan, Haolei; Li, Guo; Su, Zhi; Ren, Shuling; Zhu, Guanghao; Tian, Yongquan; Qiu, Yuanzheng; Zhang, Xin

doi:10.1016/j.canlet.2013.09.033

Cited by 49 publications

(87 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, it should be noted that the metastasis-promoting function of MTDH is likely to exist in other cancer types, beyond breast and prostate cancers. Several recent studies indeed showed abnormal MTDH expression was associated with lymph node metastasis and a worse prognosis in additional cancer types including laryngeal squamous cell carcinoma (31), squamous cell carcinoma of the head and neck (32), and hepatocellular carcinoma (33), and overexpression of MTDH increases experimental metastasis of hepatocellular carcinoma cells (34). …”

Section: Discussionmentioning

confidence: 99%

Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

Wan

Wei

et al. 2014

Cancer Research

View full text Add to dashboard Cite

Metadherin (MTDH) overexpression in diverse cancer types has been linked to poor clinical outcomes, but definitive genetic proof of its contributions to cancer remain incomplete. In particular, the degree to which MTDH may contribute to malignant progression in vivo is lacking. Here, we report that MTDH is amplified frequently in human prostate cancers where its expression levels are tightly correlated with prostate cancer progression and poor disease-free survival. Further, we show that genetic ablation of MTDH in the TRAMP transgenic mouse model of prostate cancer blocks malignant progression without causing defects in the normal development of the prostate. Germline deletion of Mtdh in TRAMP mice prolonged tumor latency, reduced tumor burden, arrested progression of prostate cancer at well-differentiated stages and inhibited systemic metastasis to distant organs, thereby decreasing cancer-related mortality ~10-fold. Consistent with these findings, direct silencing of Mtdh in prostate cancer cells decreased proliferation in vitro and tumor growth in vivo, supporting an epithelial cell-intrinsic role of MTDH in prostate cancer. Together, our findings establish a pivotal role for MTDH in prostate cancer progression and metastasis and define MTDH as a therapeutic target in this setting.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

Wan

Wei

et al. 2014

Cancer Research

View full text Add to dashboard Cite

show abstract

“…The speculation that AFX (with its essentially benign clinical behavior) represents the end result of squamous cell carcinoma (with its well-known metastatic potential) undergoing EMT may not conform to the well-documented association in the literature between EMT and an increased propensity for metastasis. Namely, EMT is widely considered to play a pivotal role in promoting metastasis in epithelial-derived malignancies [106][107][108][109][110]. Also, poor differentiation among cutaneous squamous cell carcinomas confers an aggressive behavior, yet AFX usually has a comparatively benign clinical behavior.…”

Section: A Speculative View About Afx and Epithelial-mesenchymal Transimentioning

confidence: 99%

Atypical fibroxanthoma: new insights

Hussein

2014

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

Atypical fibroxanthoma (AFX) is an ultraviolet radiation-associated dermal neoplasm. To address the clinicopathologic and molecular features of this particular neoplasm. The author conducted a literature review using PubMed searching for articles relating to AFX. AFX usually appears as a rapidly growing nodular or nodulo-ulcerative lesion. It occurs on sun-exposed skin of elderly peoples. AFX may be composed predominantly of pleomorphic, spindle, epithelioid cells, or admixture of these cells. The differential diagnosis of AFX includes pleomorphic dermal sarcoma, squamous cell carcinoma, malignant melanoma and leiomyosarcoma. Several observations favor a mesenchymal origin for AFX. These reviews address the clinicopathologic features, molecular pathology, prognosis and treatment of this neoplasm.

show abstract

“…The pathogenesis of MTDH in tumors may be interpreted as participating in signal transduction pathways, including NF-κB, Ha-ras and AKT. These signaling pathways may be involved in carcinogenesis, metastasis and progression in malignancies, predicting that MTDH may be a biomarker in cancers (7,25,26).…”

Section: Progression and Survival Of Mtdh In Prostate Cancermentioning

confidence: 99%

Metadherin in prostate, bladder, and kidney cancer: A systematic review

Zhao

Wei

Gao

et al. 2014

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Metadherin (MTDH) has been identified as an important oncogene in carcinogenesis, tumor progression and metastasis in numerous malignancies, through signal transduction pathways. MTDH is a potential biomarker and therapeutic target in cancers. The present systematic review was performed to search for studies regarding MTDH and prostate, bladder and kidney cancer using several databases and the eligible studies were reviewed. MTDH expression was found to significantly increase in prostate, bladder and kidney cancers, not only in clinical tissue samples, but also in cancer cell lines. Reviewing the clinical and statistical analysis revealed that MTDH may be involved in urologic cancer progression, metastasis and prognosis. MTDH may be an independent or one of the cofactors in urologic cancers for prediction of patient survival, and may be involved in potential anticancer strategies. MTDH may be associated with several signal transduction pathways in urologic cancers, indicating latent targets to develop anticancer therapeutic strategy. Further studies are required to confirm these findings. IntroductionMetadherin (MTDH), also known as astrocyte-elevated gene (AEG)-1 and lysine-rich CEACAM-1-associated protein (LYRIC) (1-2), was first identified in human fetal astrocytes induced by human immunodeficiency virus-1 in 2002 (3). MTDH has been cloned for nearly ten years (4-6) and is considered to be an important oncogene in carcinogenesis, tumor progression and metastasis, via a series of signaling pathways (7-9). However, as the exact functions of MTDH in cancer remain unclear, particularly in malignant tumors, future investigations are required (10).Recent studies have shown that high expressions of MTDH are present in various tumors, involving the nervous, urogenital, respiratory and digestive systems (9,(11)(12)(13)(14)(15)(16)(17)(18)(19). Evidence indicates that MTDH knockdown significantly inhibited the growth of gastric cancer cells (9). MTDH is an anti-apoptotic gene in glioma cells and could be used as a target of microRNA-136 in anticancer therapeutic strategy (11). A study revealed that MTDH promotes invasion and metastasis through the activation of nuclear factor-κB (NF-κB), interleukin-8 and matrix metalloproteinase-9 in breast cancer (12), which is consistent with studies in non-small cell lung cancer and glioma (13,14). MTDH has been shown to be associated with a poor prognosis in malignancies, including non-small cell lung cancer, invasive breast cancer, laryngeal squamous cell carcinoma, gallbladder adenocarcinoma, tongue carcinoma and bladder cancer (15)(16)(17)(18)(19). MTDH is also associated with the prognosis of carcinoma, possibly due to chemoresistance and radiosensitivity in cancer therapy (20,21).Increasing evidence indicates that MTDH is an important mediator in signal transduction pathways in malignancies, a potential biomarker to predict cancer survival and provides information to develop target chemotherapies. The present systematic review aimed to investigate the expression, pa...

show abstract

Metadherin regulates metastasis of squamous cell carcinoma of the head and neck via AKT signalling pathway-mediated epithelial–mesenchymal transition

Cited by 49 publications

References 37 publications

Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

Atypical fibroxanthoma: new insights

Metadherin in prostate, bladder, and kidney cancer: A systematic review

Contact Info

Product

Resources

About