Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

SET and MYND domain-containing protein 3 (SMYD3) plays a key role in the progression of human cancer. Matrix metalloproteinase (MMP)-9 is being related to tumor progression. It has been reported that SMYD3 and MMP-9 are overexpressed in human cancers. However, the exact roles of SMYD3 and MMP-9 in the metastasis and prognosis of gastric cancer (GC) remain unclear. The expressions of SMYD3 and MMP-9 were detected by semiquantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, SMYD3 and MMP-9 expressions were analyzed by immunohistochemistry in formalin-fixed samples from 186 gastric cancer patients. The messenger RNA (mRNA) and protein expression levels of SMYD3 and MMP-9 in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of SMYD3 was correlated with size of primary tumor and lymph node metastasis, while size of primary tumor and serosal invasion were identified as the independently relative factors of MMP-9 expression in GC tissues. SMYD3 expression and MMP-9 expression in GC tissues were significantly and positively correlated. Multivariate analysis results demonstrated that degree of differentiation, lymph node metastasis, TNM stage, SMYD3 expression, and MMP-9 expression were the independent prognostic indicators of gastric cancer. SMYD3 and MMP-9 may play important roles in tumor invasion, metastasis, and prognosis and could work as promising targets for prognostic prediction in gastric cancer.

Related collections

Most cited references 23

Record: found
Abstract: found
Article: not found

SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells.

Ryuji Hamamoto, Yoichi Furukawa, Masashi Morita … (2004)

Colorectal and hepatocellular carcinomas are some of the leading causes of cancer deaths worldwide, but the mechanisms that underly these malignancies are not fully understood. Here we report the identification of SMYD3, a gene that is over-expressed in the majority of colorectal carcinomas and hepatocellular carcinomas. Introduction of SMYD3 into NIH3T3 cells enhanced cell growth, whereas genetic knockdown with small-interfering RNAs (siRNAs) in cancer cells resulted in significant growth suppression. SMYD3 formed a complex with RNA polymerase II through an interaction with the RNA helicase HELZ and transactivated a set of genes that included oncogenes, homeobox genes and genes associated with cell-cycle regulation. SMYD3 bound to a motif, 5'-CCCTCC-3', present in the promoter region of downstream genes such as Nkx2.8. The SET domain of SMYD3 showed histone H3-lysine 4 (H3-K4)-specific methyltransferase activity, which was enhanced in the presence of the heat-shock protein HSP90A. Our findings suggest that SMYD3 has histone methyltransferase activity and plays an important role in transcriptional regulation as a member of an RNA polymerase complex. Furthermore, activation of SMYD3 may be a key factor in human carcinogenesis.

0 comments Cited 237 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer.

Roopali Roy, Jiang Yang, Marsha A Moses (2009)

The matrix metalloproteinase (MMP) family of enzymes is comprised of critically important extracellular matrix remodeling proteases whose activity has been implicated in a number of key normal and pathologic processes. The latter include tumor growth, progression, and metastasis as well as the dysregulated angiogenesis that is associated with these events. As a result, these proteases have come to represent important therapeutic and diagnostic targets for the treatment and detection of human cancers. In this review, we summarize the literature that establishes these enzymes as important clinical targets, discuss the complexity surrounding their choice as such, and chronicle the development strategies and outcomes of their clinical testing to date. The status of the MMP inhibitors currently in US Food and Drug Administration approved clinical trials is presented and reviewed. We also discuss the more recent and successful targeting of this enzyme family as diagnostic and prognostic predictors of human cancer, its status, and its stage. This analysis includes a wide variety of human cancers and a number of human sample types including tissue, plasma, serum, and urine.

0 comments Cited 212 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Changing views of the role of matrix metalloproteinases in metastasis.

A Chambers, L M Matrisian (1997)

Metastatic spread of cancer continues to be the greatest barrier to cancer cure. Understanding the molecular mechanisms of metastasis is crucial for the design and effective use of novel therapeutic strategies to combat metastases. One class of molecules that has been repeatedly implicated in metastasis is the matrix metalloproteinases (MMPs). In this review, we re-examine the evidence that MMPs are associated with metastasis and that they make a functional contribution to the process. Initially, it was believed that the major role of MMPs in metastasis was to facilitate the breakdown of physical barriers to metastasis, thus promoting invasion and entry into and out of blood or lymphatic vessels (intravasation, extravasation). However, recent evidence suggests that MMPs may have a more complex role in metastasis and that they may make important contributions at other steps in the metastatic process. Studies using intravital videomicroscopy, as well as experiments in which levels of MMPs or their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are manipulated genetically or pharmacologically, suggest that MMPs are key regulators of growth of tumors, at both primary and metastatic sites. On the basis of this evidence, a new view of the functional role of MMPs in metastasis is presented, which suggests that MMPs are important in creating and maintaining an environment that supports the initiation and maintenance of growth of primary and metastatic tumors. Further clarification of the mechanisms by which MMPs regulate growth of primary and metastatic tumors will be important in the development of novel therapeutic strategies against metastases.