Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite advances in diagnosis and treatment of prostate cancer, development of metastases remains a major clinical challenge. Research efforts are dedicated to overcome this problem by understanding the molecular basis of the transition from benign cells to prostatic intraepithelial neoplasia (PIN), localized carcinoma, and metastatic cancer. Identification of proteins that inhibit dissemination of cancer cells will provide new perspectives to define novel therapeutics. Development of antimetastatic drugs that trigger or mimic the effect of metastasis suppressors represents new therapeutic approaches to improve patient survival. This review focuses on different biochemical and cellular functions of metastasis suppressors known to play a role in prostate carcinogenesis and progression. Ten putative metastasis suppressors implicated in prostate cancer are discussed. CD44s is decreased in both PIN and cancer; Drg-1, E-cadherin, KAI-1, RKIP, and SSeCKS show similar expression between benign epithelia and PIN, but are downregulated in invasive cancer; whereas, maspin, MKK4, Nm23 and PTEN are upregulated in PIN and downregulated in cancer. Moreover, the potential role of microRNA in prostate cancer progression, the understanding of the cellular distribution and localization of metastasis suppressors, their mechanism of action, their effect on prostate invasion and metastasis, and their potential use as therapeutics are addressed.
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PMID:Metastasis suppressors in human benign prostate, intraepithelial neoplasia, and invasive cancer: their prospects as therapeutic agents. 2288 31

Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research.
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PMID:Metastasis suppressor proteins in cutaneous squamous cell carcinoma. 2721 90


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