Abstract:
:We have previously shown that the genotoxin-induced apoptosis in mouse embryo fibroblasts was enhanced by the extracellular matrix protein fibronectin (FN). In the present study, we tested the hypothesis that FN regulates the DNA damage response (DDR) signaling pathways in HCT116 (p53-wt) and HT29 (p53-mut) human colon cancer cells and tumor-derived myofibroblasts. DNA damage recognition mechanisms were analyzed by immunofluorescence staining, cell cycle analysis and immunoblotting addressed at specific molecular sensors and executors involved in the DDR pathways. The results show that FN, but not collagen type IV or Matrigel, initiates and potentiates the DDR to the anticancer drug cisplatin in an α5 integrin and cell cycle-dependent manner (S and G2/M phases) in human colon cancer cells. Accordingly, we demonstrate that adhesion of HCT116 cells to FN upregulated the expression of α5 integrin FN receptors at the cell surface. These FN-induced DDR pathways include the concerted phosphorylation of histone H2AX on Ser139 detected as nuclear foci (γ-H2AX, 15 and 25 kDa forms), of ataxia telangiectasia mutated (ATM-Ser1981), checkpoint kinase 2 (CHK2-Thr68, 62 and 67 kDa) and p53-Ser15. These FN-induced γ-H2AX signals were interrupted or attenuated by selective inhibitors acting on the DDR pathway kinases, including wortmannin (targeting the phosphatidylinositol-3-kinase-related protein kinases, PIKK), KU55933 (ATM), NU7026 (DNA-dependent protein kinase catalytic subunit, DNA-PK-cs) and SP600125 (JNK2, stress activated protein kinase/c-Jun N-terminal kinase-2). Adhesion to FN also potentiated the γ-H2AX signals and the cytotoxic effects of cisplatin in human colon tumor-derived myofibroblasts. These data provide evidence that FN promotes DNA damage recognition and chemosensitization to cisplatin via the potentiation of the DNA damage signaling responses in human colon cancer cells and tumor-derived myofibroblasts.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
DE Wever O,Sobczak-Thépot J,Vercoutter-Edouart AS,Michalski JC,Ouelaa-Benslama R,Stupack DG,Bracke M,Wang JYJ,Gespach C,Emami Sdoi
10.3892/ijo.2011.1034subject
Has Abstractpub_date
2011-08-01 00:00:00pages
393-400issue
2eissn
1019-6439issn
1791-2423journal_volume
39pub_type
杂志文章abstract::Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.3848
更新日期:2017-03-01 00:00:00
abstract::Elderly patients with advanced non-small cell lung cancer (NSCLC) require chemotherapy that is effective and minimally toxic. We evaluated the activity of a combination of vinorelbine and 5-fluorouracil (5-FU)/UFT (a fixed combination of tegafur and uracil) in vitro and in vivo to establish a rationale for clinical us...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract::Early detection and treatment are critical in the management of renal cell carcinoma (RCC). However, there is no standard serum biomarker to facilitate early diagnosis or prognostic stratification in patients with RCC. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for di...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2169
更新日期:2014-01-01 00:00:00
abstract::It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum L. Gaertn.), to mouse skin prevents photocarcinoge...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-12-01 00:00:00
abstract::Previous studies from this laboratory have shown that bioflavonoids including luteolin and quercetin possess antiestrogenic activity in the female reproductive tract and appear to elicit this activity by interaction with type II [H-3]estradiol binding sites in the cell nucleus. Studies by a number of laboratories incl...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.6.1311
更新日期:1997-12-01 00:00:00
abstract::Lung cancer is the most common and most lethal type of cancer. A sustained proliferative capacity is one of the hallmarks of cancer, and microtubules serve an important role in maintaining a sustained cell cycle. Therefore, understanding the regulation of microtubule proteins in the cell cycle is important for tumor p...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4805
更新日期:2019-07-01 00:00:00
abstract::Hepatocyte growth factor (HGF), the ligand for the c-met proto-oncogene product, is a multifunctional protein that enhances tumor cell motility, extracellular matrix invasion, and mitogenic or morphogenic activities of various cell types. In this study we examined the expression of the c-Met receptor in human oral squ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::Although a correlation between anaplasia and mutations of the p53 tumor suppressor gene has been found in Wilms' tumor (WT) a prognostic significance of p53 in WT remains largely unresolved. The goal of this study was to obtain a better understanding of the role of p53 expression in WT. Immunohistochemical analysis wa...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::A number of glycosyltransferases have been identified and biologically characterized in cancer cells, yet their exact pathophysiological functions are largely unknown. Here, we report the critical role of β1,3-N-acetylgalactosaminyltransferase II (B3GALNT2), which transfers N-acetylgalactosamine (GalNAc) in a β1,3 lin...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2187
更新日期:2014-02-01 00:00:00
abstract::MicroRNA (miRNA or miR) inhibition of oncogenic related pathways has been shown to be a promising therapeutic approach for cancer. SIRT1 might be a promoter factor on tumorigenesis of hepatocellular carcinoma (HCC). However, the mechanism is unknown. We investigated whether miRNAs regulate the SIRT1 and its downstream...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2596
更新日期:2014-11-01 00:00:00
abstract::Glioblastomas are highly vascularized tumors and anti-angiogenic strategy is one of the most promising therapeutic approaches to treat brain tumors. Interferon alpha (IFN-alpha) as a single agent or combined with standard chemo-therapy has been shown to inhibit various tumors, but the effect of combination anti-angiog...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-06-01 00:00:00
abstract::Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in epithelial tumor carcinogenesis. In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the induction of RON and tumor growth in human gastric cancer. EGCG i...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1775
更新日期:2013-03-01 00:00:00
abstract::Human breast epithelial MCF10AT cells injected with Matrigel into the subcutis of nude/beige mice form simple ducts which, with time, resemble human proliferative breast disease and sporadically progress to carcinoma. Basement membrane was visualized with a silver stain and myoepithelial cells detected by their reacti...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.9.2.263
更新日期:1996-08-01 00:00:00
abstract::Hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC) is a global health problem that accounts for more than half of total liver cancer cases in developing countries. Despite the growing number of researches conducted, the molecular mechanism underlying the development of HCC remains elusive. Long non‑coding ...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2019.4909
更新日期:2020-01-01 00:00:00
abstract::Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome involving a predisposition to cancers of the colon, endometrium and several other extra-colonic sites, accounting for approximately 1-5% of all colorectal cancer cases. It is not easily recognized because of a lack of distinctive clinical markers, making ...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.12.4.947
更新日期:1998-04-01 00:00:00
abstract::A serum-specific protein 'fingerprint' model was established which is capable of evaluating the effect of chemotherapy (gemcitabine) of pancreatic adenocarcinoma. We used SELDI-TOF-MS coupled with CM10 chips and bioinformatics tools to analyze a total of 45 mouse serum samples from three groups: the healthy control gr...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000804
更新日期:2010-12-01 00:00:00
abstract::Gamma linolenic acid (GLA) is an anti-cancer agent recently reported to inhibit tumour cell-matrix attachment. This study examined the effects of GLA on the adhesion of two tumour cell lines, HT115 (human colon) and MDA MB 231 (human breast), to an extracellular matrix, Matrigel. The action of GLA on focal adhesion ki...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.3.583
更新日期:1996-03-01 00:00:00
abstract::The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presen...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1031
更新日期:2011-07-01 00:00:00
abstract::5-Fluorouracil (5-FU), often used in combination with levofolene (LF), can induce, as an important side effect, the hand-foot syndrome (HFS) due to toxicity on keratinocytes. This can also damage workers involved in its handling. In the present study, we investigated the mechanisms of the toxicity induced by 5-FU alon...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2904
更新日期:2015-05-01 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::Targeting protein kinases as a therapeutic approach to treat various diseases, especially cancer is currently a fast growing business. Although many inhibitors are available, exhibiting remarkable potency, the major challenge is their selectivity. Here we show that the protein kinase CK2 inhibitors DMAT, TBB and resor...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000431
更新日期:2009-11-01 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::We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells. ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-04-01 00:00:00
abstract::Chemotherapeutic treatment with combinations of drugs is front-line therapy for many types of cancer. Combining drugs that target different signaling pathways often lessens adverse side-effects while increasing the efficacy of treatment and reducing patient morbidity. Histone deacetylase (HDAC) inhibitors represent a ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-05-01 00:00:00
abstract::One of the early events of apoptosis is proteolysis. The enzyme(s) involved in this event appear to be the serine protease(s), inasmuch as the reversible or irreversible inhibitors of serine proteases prevent DNA degradation and abrogate other signs of apoptosis in several cell systems (Gorczyca et al, Int J Oncol 1: ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.4.627
更新日期:1993-10-01 00:00:00
abstract::As epidemiological data suggest ultraviolet (UV) radiation to be the major environmental factor for the development of melanoma, we screened this malignancy for UV-specific C right curved arrow T and CC right curved arrow TT DNA mutations as described in squamous and basal cell carcinomas of the skin. Mitochondrial (m...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract::Malignant peripheral nerve sheath tumor (MPNST) is a rare malignant tumor, for which only a few cultured cell lines are available to date. In the present study, we established three new MPNST cell lines, FU-SFT8611, FU-SFT8710 and FU-SFT9817, from a 40-year-old Japanese man without neurofibromatosis 1 (NF1), a 43-year...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.29.6.1421
更新日期:2006-12-01 00:00:00
abstract::The purpose of this study was to determine whether the synthesis of endogenous nitric oxide (NO) is involved in the apoptosis of murine L929 transformed fibroblasts. L929 parental cells and L929 cells selected for resistance to tumor necrosis factor (TNF-alpha) were incubated in vitro with various concentrations of TN...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.6.1043
更新日期:1993-12-01 00:00:00
abstract::Most solid tumors display extracellular acidosis, which only partially overlaps with hypoxia and induces distinct adaptive changes leading to aggressive phenotype. Although acidosis is mainly attributable to excessive production of lactic acid, it also involves carbonic anhydrase (CA) IX-mediated conversion of CO(2) t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-10-01 00:00:00
abstract::Transcriptional silencing of the DNA repair protein, O6-methylguanine-DNA methyltransferase (MGMT), occurs only in malignant or transformed cell lines, and such MGMT-deficient cells are hypersensitive to chemotherapeutic alkylating agents such as 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide. Previous...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.18.6.1187
更新日期:2001-06-01 00:00:00