Down-regulated expression of SERPIN genes located on chromosome 18q21 in oral squamous cell carcinomas

Shiiba, Masashi; Nomura, Hitomi; Shinozuka, Keiji; Saito, Kengo; Kouzu, Yukinao; Kasamatsu, Atsushi; Sakamoto, Yosuke; Murano, Akiyuki; Ono, Kumeo; Ogawara, Katsunori; Uzawa, Katsuhiro; Tanzawa, Hideki

doi:10.3892/or_00000852

Cited by 34 publications

(27 citation statements)

References 20 publications

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“…SERPINB13 was found to be down-regulated in squamous-cell carcinoma of the oral cavity and in squamous-cell carcinoma cell lines of head and neck cancer (17), but up-regulated in skin carcinoma (18,19). Recently, decreased expression of SERPIN genes including SERPINB2, SERPINB3, SERPINB4, SERPINB7, SERPINB11, SERPINB12 and SERPINB13 on chromosome 18q21 has been demonstrated in oral squamous-cell carcinomas, while the T/N (tumor vs. matched normal tissues) expression ratio of these SERPIN genes was found to have no significant association with clinicodemographic characteristics (20). Apart from the previously mentioned members of the human SERPINB family, however, whether the remaining members, such as SERPINB2 and SERPINB5, are associated with cancer and whether they are functionally important in cancer metastasis, are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Suppression of the invasion and migration of cancer cells by SERPINB family genes and their derived peptides

et al. 2011

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Abstract.Apart from SERPINB2 and SERPINB5, the roles of the remaining 13 members of the human SERPINB family in cancer metastasis are still unknown. In the present study, we demonstrated that most of these genes are differentially expressed in tumor tissues compared to matched normal tissues from lung or breast cancer patients. Overexpression of each SERPINB gene effectively suppressed the invasiveness and motility of malignant cancer cells. Among all of the genes, the SERPINB1, SERPINB5 and SERPINB7 genes were more potent, and the inhibitory effect was further enhanced by co-expression of any two of them. In addition, single treatment of the synthetic peptides corresponding to the P5-P5' sequences of the reactive center loop (RCL) of SERPINB1, SERPINB5 or SERPINB7 markedly suppressed the invasive and migratory properties of the cancer cells in a dose-dependent manner. More significantly, combination treatment of these peptides in cancer cells further improved the suppressive effect by 20-40%. Here, we determined the expression of all SERPINB family members in lung and breast cancer patients, and identified those members with potent inhibitory ability toward invasion and migration, and designed RCL-derived peptides to suppress the malignancy of cancer cells. Forced re-expression of these anti-invasive SERPINB genes or application of the SERPINB RCL-peptides may provide a reasonable strategy against lethal cancer metastasis. IntroductionCancer metastasis is the leading cause of morbidity and mortality in cancer patients. It is a highly complex process, including cell detachment, migration, invasion, circulation in blood vessels, adhesion, colonization at other sites and formation of secondary tumors (1). Prior to tumor cell detachment from the primary site, which leads to cell migration and invasion in the metastasis process, the extracellular matrix (ECM) microenvironment must be degraded by proteases, such as urokinase plasminogen activator (uPA), uPA receptor (uPAR) and the plasmin network (2,3) and matrix metalloproteinases (MMPs) (4). On the other hand, protease inhibitors negatively regulate the proteolysis process in cancer metastasis, e.g. plasminogen activator inhibitors (PAIs), PAI-1 (SERPINE1) and PAI-2 (SERPINB2) against uPA/uPAR/plasmin network and the tissue inhibitor of matrix metalloproteinases (TIMPs), TIMP-1 to TIMP-4 against MMPs.Serine protease inhibitors (serpins) regulate many physiological processes, such as blood coagulation, fibrinolysis, inflammation, complement activation and cell migration (5). Based on their phylogenic relationships, the superfamily is divided into 16 different clades (A-P), in which human serpins are the first 9 clades (A-I) (6). The clade B serpins (SERPINB family) is the largest one within the human serpin superfamily. It contains 13 genes located on chromosome 6p25 (SERPINB1, SERPINB6 and SERPINB9) and 18q21 (the remaining members of the family). Unlike circulating serpins, the SERPINB family genes lack the N and C terminus extension regions common to other serpin...

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Section: Introductionmentioning

confidence: 99%

Suppression of the invasion and migration of cancer cells by SERPINB family genes and their derived peptides

et al. 2011

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“…Most serpins act as inhibitors of chymotrypsin-like SPs, others as cross-class serine protease inhibitors of papain-like cysteine proteases and caspases (10)(11)(12)(13). Certain serpins have been identified to be involved in the progression of malignant tumor; these include SERPINB3 and SERPINB4 in squamous cell carcinoma (14,15), SERPINB5 in human breast cancer (16), SERPINB13 in head and neck squamous cell carcinoma (17), SERPINH1 in head and neck carcinomas (18), SERPINI2 in breast cancer (19), SERPINB2 and SERPINE1 in breast cancer and other cancers (20), and SERPINB2, SERPINB3, SERPINB4, SERPINB7, SERPINB11, SERPINB12 and SERPINB13 in oral squamous cell carcinoma (21).…”

Section: Introductionmentioning

confidence: 99%

Development of a survival prediction model for gastric cancer using serine proteases and their inhibitors

Lei

Liu

Zhang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Proteolytic enzymes play a key role in the metastatic stage of gastric cancer (GC). In this study, we aimed to identify the serine proteases (SPs) and their inhibitors (serpins) as related to GC. The gene expression profiles of 40 cases of GC were initially detected by cDNA microarray. The results of the differentially expressed SPs and their inhibitor genes from the microarrays were confirmed by real-time PCR. The status of the immunohistochemical staining of the confirmed genes in patients with complete data was used to develop a survival prediction model. Finally, the prediction model was tested in different groups of GC patients. As a result, seven genes, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8, were considered as GC progression-related genes. A survival prediction model including the immunohistochemical scores of three genes and the tumor node metastasis (TNM) score was developed: Survival time (months) = 88.8607 + 2.6395 SERPINB5 -12.0772 KLK10 + 13.7562 KLK11 -7.0318 TNM. In conclusion, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8 were GC progression-related SPs or serpin genes. The model consisting of the expression profiles of three genes extracted from the microarray study accompanied by the TNM score accurately predicts surgeryrelated survival of GC patients.

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“…Consistently, downregulation of SLC25A47 has been shown to induce the dissipation of the mitochondrial membrane potential in hepatocellular carcinoma, a common phenomenon observed in cancer cells (24). SERPINA11 is correlated with pathological stage of hepatocellular carcinoma, and is downregulated in oral squamous cell carcinomas (25). Thus, these genes could be a potential therapeutic target and biomarker in the treatment of iCCA.…”

Section: Discussionmentioning

confidence: 57%

Overexpression of PDZK1IP1, EEF1A2 and RPL41 genes in intrahepatic cholangiocarcinoma

Yang

Zong

2016

Molecular Medicine Reports

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Abstract. Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy in the liver, which is associated with a poor prognosis. However, the molecular pathogenesis of iCCA remains unclear. RNA-Seq for tumor and para-tumor sample pairs enables the characterization of changes in the gene expression profiles of patients with iCCA. The present study analyzed RNA-Seq data of seven iCCA para-tumor and tumor sample pairs. Differential gene expression analysis demonstrated significant upregulation of PDZK1IP1, EEF1A2 and RPL41 (ENSG00000279483) genes in the iCCA samples when compared with the matched para-tumor samples. Furthermore, genes associated with the immune system, metabolism and metabolic energy were significantly downregulated in the iCCA tumor tissues, indicating that this is involved in the pathogenesis of iCCA. The present study aimed to elucidate the gene expression patterns associated with the tumorigenesis of iCCA by comparing tumor and normal tissues, in order to isolate novel diagnostic factors for iCCA.

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Down-regulated expression of SERPIN genes located on chromosome 18q21 in oral squamous cell carcinomas

Cited by 34 publications

References 20 publications

Suppression of the invasion and migration of cancer cells by SERPINB family genes and their derived peptides

Suppression of the invasion and migration of cancer cells by SERPINB family genes and their derived peptides

Development of a survival prediction model for gastric cancer using serine proteases and their inhibitors

Overexpression of PDZK1IP1, EEF1A2 and RPL41 genes in intrahepatic cholangiocarcinoma

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