Abstract:
:Dickkopf‑related protein 3 (DKK3), which is a member of the Dickkopf WNT signaling pathway inhibitor family, is considered to be a tumor suppressor, due to its reduced expression in cancer cells and its ability to induce apoptosis when overexpressed by adenovirus. However, our previous study demonstrated alternative functions for DKK3 in head and neck squamous cell carcinoma (HNSCC). Our study reported that DKK3 expression was predominantly upregulated in HNSCC cell lines and tissue samples, and its expression was significantly correlated with poor prognosis. Furthermore, DKK3 overexpression in HNSCC cells significantly increased cancer cell proliferation, migration, invasion and in vivo tumor growth. These data have led to the hypothesis that DKK3 may exert oncogenic functions and may increase the malignant properties of HNSCC. The present study established a stable DKK3 knockdown cell line (HSC‑3 shDKK3) using lentivirus‑mediated short hairpin RNA, and assessed its effects on cancer cell behavior using MTT, migration and invasion assays. In addition, its effects on in vivo tumor growth were assessed using a xenograft model. Furthermore, the molecular mechanisms underlying the effects of DKK3 knockdown were investigated by microarray analysis, pathway analysis and western blotting. Compared with control cells, HSC‑3 shDKK3 cells exhibited significantly reduced proliferation, migration and invasion, and formed significantly smaller tumor masses when subcutaneously transplanted into nude mice. In addition, in HSC‑3 shDKK3 cells, the expression levels of phosphorylated (p)‑protein kinase B (Akt) (Ser473), p‑phosphoinositide 3‑kinase (PI3K) p85 (Tyr467), p‑PI3K p55 (Try199), p‑3‑phosphoinositide‑dependent protein kinase‑1 (PDK1) (Ser241) and total p38 mitogen‑activated protein kinase (MAPK) were reduced. Furthermore, phosphorylation of mechanistic target of rapamycin (mTOR) (Ser2448) was slightly decreased in HSC‑3 shDKK3 cells, which may be due to the increased expression of DEP domain‑containing mTOR‑interacting protein. Conversely, DKK3 overexpression in HSC‑3 shDKK3 cells rescued cellular proliferation, migration and invasion. With regards to expression levels, p‑PI3K and p‑PDK1 expression was not altered, whereas mTOR and p‑p38 MAPK expression was elevated. These data supported the hypothesis and indicated that DKK3 may contribute to the malignant phenotype of HNSCC cells via the PI3K/Akt/mTOR and MAPK signaling pathways.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Katase N,Nishimatsu SI,Yamauchi A,Yamamura M,Fujita Sdoi
10.3892/ijo.2018.4667subject
Has Abstractpub_date
2019-03-01 00:00:00pages
1021-1032issue
3eissn
1019-6439issn
1791-2423journal_volume
54pub_type
杂志文章abstract::Overexpression of TMPRSS4, a cell surface-associated transmembrane serine protease, has been reported in pancreatic, colorectal and thyroid cancers, and has been implicated in tumor cell migration and metastasis. Few reports have investigated both TMPRSS4 gene expression levels and ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1513
更新日期:2012-09-01 00:00:00
abstract::The inhibitor of oxidative phosphorylation, 2,4-dinitrophenol (DNP), abrogates etoposide cytotoxicity in murine leukemia L1210 cells without affecting the quantity of drug-induced DNA lesions. Cell cycle arrest and events associated with cell death were followed in etoposide treated L1210 cells under conditions in whi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.2.305
更新日期:1996-02-01 00:00:00
abstract::Clinicopathological assessment of the functional relationship between the HER2 oncogene and tumor-associated fatty acid synthase (FASN) is largely precluded because immunohistochemical and/or mRNA studies should be performed in biopsies from breast cancer patients. We here sought to determine whether serum FASN (sFASN...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000455
更新日期:2009-12-01 00:00:00
abstract::Alphaviruses have several characteristics that make them attractive as gene therapy vectors such as transient and high-level expression of a heterologous gene. Alphavirus vectors, Semliki Forest virus (SFV), Sindbis virus (SIN) and Venezuelan equine encephalitis virus (VEE) have been developed as gene expression vecto...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2004-04-01 00:00:00
abstract::Although histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. This study was undertaken to investigate the underlying mechanism of an HDAC inhibitor, Trichostatin A (TSA), -induce...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-08-01 00:00:00
abstract::High consumption of soy products in some Asian countries has been linked to the low incidence of breast cancer in women. The chemopreventive effect of the soy isoflavone, genistein, has been observed through the suppression of cell proliferation, inhibition of angiogenesis and stimulation of apoptosis in breast carcin...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract::Gene expression of dihydropyrimidine dehydrogenase (DPD) and newly multidrug resistance-associated protein (MRP) was found to correlate well with primary 5-FU resistance in 7 human gastrointestinal cancer cell lines. Although mRNA and protein levels of thymidylate synthase (TS) did not relate to the resistance, 5-FU t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.3.551
更新日期:1999-03-01 00:00:00
abstract::Expression of the tumor suppressor gene p53 and the ras oncogene were examined in 46 tumor and nodal specimens of non-small cell lung cancer (NSCLC) using the antibodies p53 pAb 240 and ras Y13-259 respectively. p53 expression was elevated in 46% and ras p21 was over-expressed in 85% of the tumor specimens analyzed. F...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.1.4.403
更新日期:1992-09-01 00:00:00
abstract::We examined the expression levels of P-glycoprotein (P-Gp)/the human multidrug resistance gene (MDR1) and in vivo chemosensitivity in the 7 osteosarcoma xenografts. Three of seven (43%) osteosarcoma xenografts expressed MDR1 by reverse transcriptase-polymerase chain reaction (RT-PCR). The OSS-516R xenograft selected w...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Identification of sensitive and specific biomarkers for early detection and prognosis of prostate cancer is essential for timely and appropriate treatment of the disease in individual patients. We identified an RNA transcript with sequence homology to TRPM8 (melastatin-related transient receptor potential member 8) th...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2010-02-01 00:00:00
abstract::Gene amplification occurs frequently in human glioblastomas. We report the amplification and expression analysis of glioma amplified sequence 64 (GAS64) which was recently identified by microdissection mediated cDNA capture from the amplicon at 12q13-15. Herein we analyzed primary tumor tissues for amplification frequ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Loss of E-cadherin and catenin expression may be associated with distant and lymph node metastases in breast cancer. Heterogeneity of E-cadherin expression is associated with poor prognosis, suggesting that E-cadherin and catenins may serve as useful prognostic markers for invasive breast carcinoma. Reduction or loss ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::MicroRNAs can govern up to hundred different mRNAs and are important regulators of gene expression programs in development and disease. We analyzed the expression of microRNA-21, one of the most common oncomirs, in non-small cell lung cancer (NSCLC). Using northern blots the microRNA-21 expression levels of NSCLC-deri...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2272
更新日期:2014-04-01 00:00:00
abstract::Idarubicin (IDA) is a 4-demethoxy-anthracycline analogue of daunorubicin (DNR). IDA has been recognized as a potent anti-leukemic agent. However, the molecular mechanism of IDA-induced cell death remains unclear. In the present study, we investigated the activity of IDA to induce apoptosis in human leukemia HL-60 and ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Quantitative nuclear morphometry (QNM) provides a reliable, reproducible method for measuring the degree of nuclear pleomorphism, a qualitative parameter widely incorporated into histopathological grading schemes. Nuclear shape has successfully been shown to predict primary prostate adenocarcinoma metastatic potential...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.7.3.673
更新日期:1995-09-01 00:00:00
abstract::Functional defects in DNA mismatch repair genes have been shown to be associated mainly with hereditary human malignancies. We examined genomic DNA from 88 sporadic transitional cell carcinomas (TCCs) of the urinary tract for mutations in hMSH6 gene by polymerase chain reaction and direct sequencing analysis. Mutation...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::There is increasing evidence that different types of breast cancers are related to distinct risk factors. We analyzed the risk of breast cancer with respect to circulating insulin-like growth factor (IGF)-I, IGF-binding protein (IGFBP)-3, 17beta-estradiol, estrone, testosterone, androstenedione and sex hormone-binding...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-07-01 00:00:00
abstract::Oncogenic drivers of osteosarcoma remain controversial due to the complexity of the genomic background of the disease. There are limited novel therapeutic options, and the survival rate of patients with osteosarcoma has not improved in decades. Genomic instability leads to complexity in various pathways, which is pote...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4737
更新日期:2019-05-01 00:00:00
abstract::Growth and inflammatory factors are associated with poor prognosis in gastric adenocarcinoma (GA); however, the additive effects of growth and inflammatory factors in GA remain unclear. In this study, we investigated the ability of epidermal growth factor (EGF) and interleukin (IL-1β) to activate extracellular signal-...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2401
更新日期:2014-07-01 00:00:00
abstract::Human breast cancer is a major cause of global morbidity and mortality in women and it is a process that involves numerous molecular and cellular alterations attributed to environmental substances and agents such as hormones. Bisphosphonates, such as pamidronate, are potent antiresorptive drugs used to the treatment o...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2955
更新日期:2015-01-01 00:00:00
abstract::Structural maintenance of chromosome 1 alpha (SMC1A) gene has been reported to be related to tumor development in some types of human cancers. However, the misregulation of SMC1A and its functions in castration-resistant prostate cancer (CRPC) have not been well understood. In the present study, we found that SMC1A wa...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3697
更新日期:2016-11-01 00:00:00
abstract::Since the efficacy of chemotherapy can be enhanced by targeting to specific receptors on tumors, we investigated the expression of LH-RH receptors in 5 human colon cancer lines and the effects of cytotoxic LH-RH analogs on these tumors. Nude mice bearing HT-29, HCT-116, HCT-15, LoVo and Colo-320DM cancers were treated...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-06-01 00:00:00
abstract::Following the publication of this article, the authors noted that there was an error in the affiliations. Specifically, the affiliation of the first author JUAN XU should be: Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua, Zhejiang 321000, P.R. China. [the original article was publis...
journal_title:International journal of oncology
pub_type: 杂志文章,已发布勘误
doi:10.3892/ijo.2017.3977
更新日期:2017-06-01 00:00:00
abstract::Although CD138 expression is a hallmark of plasma cells and myeloma cells, reduced CD138 expression is occasionally found. However, the mechanisms underlying CD138 downregulation in myeloma cells remain unclear. Previous reports suggest that the bone marrow microenvironment may contribute to CD138 downregulation. Amon...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2134
更新日期:2013-12-01 00:00:00
abstract::Recombinant adenovirus-associated vector serotype 2 (rAAV2) is one of the most promising gene transfer vectors due to its advantage of causing non-pathogenic infection, low immunogenicity, and long-term gene expression in human clinical trials. Human interleukin 15 (hIL15) has been implicated in modulation of antitumo...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2010-02-01 00:00:00
abstract::Most tissue microarray studies have used a single 0.6-mm tissue core per donor tissue. It has been suggested that multiple cores per donor can increase the representativity of tissue microarray studies. To estimate the potential benefit of multiple cores, we analyzed Ki67 and p53 in...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1216
更新日期:2012-01-01 00:00:00
abstract::Glioblastoma multiforme (GBM) is characterized by extensive angiogenesis that is mostly orchestrated by the hypoxia inducible factor HIF-1. Deregulation of HIF-1 is believed to contribute to cancer initiation and progression. However, instances have been described in which loss of HIF-1 leads to more aggressive tumors...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000554
更新日期:2010-04-01 00:00:00
abstract::We found that a mouse p53 cDNA clone (pP53-5; Jenkins et al, Nature 312: 651-654, 1984), which previously was characterized as encoding mutant p53 protein, in fact represents wild-type mouse p53 cDNA, as we were able to demonstrate that the mutations described represented sequencing artefacts (compressions). Such sequ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.1.23
更新日期:1993-07-01 00:00:00
abstract::In a previous study, it was demonstrated that Rhein lysinate (RHL) inhibited HeLa cell proliferation via a specific mechanism. The aim of the present study was to clarify the mechanism of RHL by investigating its effect on mitochondrial damage and cell apoptosis. The results indicated that RHL inhibited cell growth an...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4554
更新日期:2018-11-01 00:00:00
abstract::The aim of the present study was to evaluate the performance of whole-body diffusion-weighted imaging (WB-DWI), whole-body positron emission tomography with computed tomography (WB-PET/CT), and whole-body positron emission tomography with magnetic resonance imaging (WB-PET/MRI) in staging patients with untreated invas...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.4012
更新日期:2017-07-01 00:00:00