Abstract:
:Hypoxia, a common phenomenon in human solid tumors, is associated with invasion and metastasis in various tumors. Hypoxia inducible factors (HIFs) are key molecules in the hypoxic response, and regulate the activation of specific genes, which mediate many of the adaptations to hypoxia. CC chemokine receptor 7 (CCR7) has been shown to play a critical role in cell chemotaxis and homing, which are key steps in cancer metastasis. A study has demonstrated that hypoxia could upregulate CCR7 in breast cancer cells. The CCR7 gene presents hypoxia response element (HRE; (A)/(G)CGTG). We presumed that hypoxia induced upregulation of HIFs promoted the expression of CCR7 facilitating tumor cells invasion and metastasis. In this study, we firstly examined the relationship of CCR7 and HIF-1alpha, HIF-2alpha in 94 cases non-small cell lung cancer (NSCLC) tissues by immunohistochemistry. The results showed that CCR7 expression correlated positively with HIF-1alpha and HIF-2alpha, all of them correlated with clinical stage and lymph node metastasis. Then, we investigated whether hypoxia induce the expression of CCR7 through HIF-1alpha and/or HIF-2alpha and observed the effects of upregulated CCR7 on the migration and invasion of lung cancer cells. We found that hypoxia induced HIF-1alpha and HIF-2alpha expression, which upregulated CCR7 expression; inhibiting HIF-1alpha or HIF-2alpha expression in BE1 and A549 cells by RNAi led to the decrease of CCR7 expression, inhibition of migratory and invasive abilities, and the effects of HIF-1alpha were more significant. Moreover, the migration and invasion of BE1 cells were increased as well as the expression of p-ERK1/2 after CCR7 transfection, but the cells invasive ability was inhibited after blocking p-ERK1/2 with PD98059 and CCR7 with specific antibody. In summary, our study demonstrated that hypoxia-HIF-1alpha, 2alpha-CCR7-ERK1/2 pathway could regulate the migration and invasion of lung cancer cells under hypoxic conditions and promote metastasis of lung cancer.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Li Y,Qiu X,Zhang S,Zhang Q,Wang Edoi
10.4161/cbt.8.4.7332subject
Has Abstractpub_date
2009-02-01 00:00:00pages
322-30issue
4eissn
1538-4047issn
1555-8576pii
7332journal_volume
8pub_type
杂志文章abstract:BACKGROUND AND AIM:H. pylori interacts with gastric epithelial cells, which may activate signaling pathways important for gastric cancer invasion. Ezrin, a membrane cytoskeletal crosslinker protein, is well documented to regulate cell adhesion and cell motility. The aim of the present study was to determine whether ezr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.8.14691
更新日期:2011-04-15 00:00:00
abstract:BACKGROUND:Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20834
更新日期:2012-08-01 00:00:00
abstract::Current risk stratification using clinical and pathological parameters in patients with urothelial carcinoma of the bladder (UCB) is insufficient. Additional information on the tumor biology can be derived from molecular biomarkers assessed in surgical UCB specimens and the predictive accuracy of oncologic end points ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.10.5.13022
更新日期:2010-09-01 00:00:00
abstract::The present studies sought to further understand how the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib interact to kill tumor cells. Sorafenib activated SRC, and via SRC the drug combination activated ERK1/2. Expression of dominant negative SRC or dominant negative MEK1 abolished drug-induced ERK1/2 ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20562
更新日期:2012-07-01 00:00:00
abstract::There is an urgent need to develop new strategies to treat ovarian cancer, the most deadly gynecologic malignancy. Histone deacetylase (HDAC) inhibitors are emerging as novel therapeutic drugs in the treatment of a variety of cancers, including those resistant to standard chemotherapy. Since there are multiple HDAC is...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.5.4007
更新日期:2007-05-01 00:00:00
abstract::Between 1955 and 1963 millions of people were worldwide vaccinated with polio-vaccines that were contaminated with the simian virus 40 (SV40). This tumor-inducing virus has subsequently been detected in several human tumors. In Austria, polio mass vaccination started in winter 1961/62 with a presumably SV40-free Briti...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
abstract::Phorbol 12-myristate 13-acetate (PMA) modulates cell proliferation and survival by activating several intracellular signaling pathways. Protein kinase C (PKC) plays a key role in PMA-induced growth arrest of non-small cell lung cancer (NSCLC) cells. Kruppel-like transcription factor 6 (KLF6), which is associated with ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.9.8186
更新日期:2009-05-01 00:00:00
abstract::Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formati...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.3.3702
更新日期:2007-03-01 00:00:00
abstract::RNA-dependent protein kinase is an interferon-induced, double-stranded (ds), RNA-activated serine/threonine protein kinase involved in the eukaryotic response to viral infection. While PKR also functions in cellular differentiation, growth control and apoptosis, its role in human cancer remains poorly understood. To e...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.3.7386
更新日期:2009-02-01 00:00:00
abstract::The role of immunotherapy in combination with traditional treatment regime in improving the survival of cancer patients has attracted more and more attention. Especially the abscopal effect that describes the phenomenon of localized radiotherapy leading to regression of distant unirradiated tumors and the role of enha...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1276133
更新日期:2017-03-04 00:00:00
abstract:BACKGROUND:Unlike papillary thyroid cancer (PTC), anaplastic thyroid carcinoma (ATC) is extremely aggressive and rapidly lethal without effective therapies. However, the differences of master regulators and regulatory networks between PTC and ATC remain unclear. Methods: Three representative datasets comprising 32 ATC,...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1803009
更新日期:2020-09-01 00:00:00
abstract::This study investigated different methods of EGFR (Epithelial Growth Factor Receptor) targeting in feline squamous cell carcinoma with the ultimate aim of establishing a large animal model of human head and neck cancer. Both small molecule receptor tyrosine kinase inhibitor (TKI) and RNA interference (RNAi) techniques...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.11.15525
更新日期:2011-06-01 00:00:00
abstract::E2F-1, a key transcription factor necessary for cell growth, DNA repair, and differentiation, is an attractive target for development of anticancer drugs in tumors that are E2F "oncogene addicted". We identified a peptide isolated from phage clones that bound tightly to the E2F-1 promoter consensus sequence. The pepti...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.25184
更新日期:2013-08-01 00:00:00
abstract::Ten years ago, a concerted effort from several labs resulted in the cloning of BRCA1, the first of two major hereditary breast/ovarian cancer predisposition genes. Since that time, BRCA1 has been linked to several key nuclear functions connected with the prevention of genomic instability. In particular, BRCA1 function...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.3.6.842
更新日期:2004-06-01 00:00:00
abstract::Numerous tyrosine kinase inhibitors (TKIs) targeting c-Met are currently in clinical trials for several cancers. Their efficacy is limited due to the development of resistance. The present study aims to elucidate this mechanism of c-Met TKI resistance by investigating key mTOR and Wnt signaling proteins in melanoma ce...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.29451
更新日期:2014-09-01 00:00:00
abstract::Sunitinib, a multi-targeted tyrosine kinase inhibitor, is frequently incorporated into the management of papillary thyroid carcinoma refractory to standard therapies. Although clinical trials are in progress, the mechanism of action in papillary thyroid carcinomas is not clear, especially regarding the effect on BRAF ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.5.16303
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Mutations that activate the PI3K/AKT/mTOR pathway are relatively common in urothelial (bladder) cancers, but how these pathway mutations affect AKT dependency is not known. We characterized the relationship between AKT pathway mutational status and sensitivity to the effects of the selective AKT kinase inhib...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.21793
更新日期:2012-11-01 00:00:00
abstract::Breast cancer is one of the most commonly diagnosed malignancies in women. Despite the remarkable success of mammography screening and use of adjuvant systemic therapy, it is estimated that approximately 200,000 new diagnoses will be made this year and 40,000 deaths will occur due to this disease (American Cancer Soci...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.9.17677
更新日期:2011-11-01 00:00:00
abstract::It was well known that cancer-associated fibroblasts (CAFs) were an essential factor in tumor progression. However, the actual mechanism of stromal fibroblasts activation and tumor promoting effects remain unclear. Here, we showed that KLF5 expression was more frequently observed in gastric cancer-associated fibroblas...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1373219
更新日期:2017-10-03 00:00:00
abstract::PRL-1 (phosphatase of regenerating liver-1), PRL-2 and PRL-3 are protein tyrosine phosphatases with a C-terminal prenylation motif that are localized to the inner leaflet of the plasma membrane and early endosomes. A variety of metastatic PRL-overexpressing cancers have been reported. Therefore, the three PRL-phosphat...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.5.5764
更新日期:2008-05-01 00:00:00
abstract::Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advan...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2017.1414757
更新日期:2018-03-04 00:00:00
abstract::Historically, ErbB3 has been overlooked within the ErbB receptor family due to its perceived lack of tyrosine kinase activity. We have previously demonstrated that in pancreatic cancer ErbB3 is the preferred dimerization partner of EGFR, ErbB3 protein expression level directly correlates with the anti-proliferative ef...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.6.12532
更新日期:2010-09-15 00:00:00
abstract::Tangeretin, a major phytochemicals in tangerine peels--an important Chinese herb, has been found to have anti-carcinogenic properties. To improve bioavailability and increase potency of tangeretin, its derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone (5-AcTMF), has been synthesized and shown potent inhibition of p...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1108491
更新日期:2016-01-01 00:00:00
abstract::Several microRNAs (miRNA) have been implicated in H. pylori related gastric cancer (GC). However, the molecular mechanism of miRNAs in gastric cancer has not been fully understood. In this study, we reported that miR-101 is significantly down-regulated in H. pylori positive tissues and cells and in tumor tissues with ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.987523
更新日期:2015-01-01 00:00:00
abstract::Mortality data by geographic area and trend-based surveillance are particularly relevant in orienting public health decisions targeting specific populations. We analyzed overall and site-specific cancer mortality between 1988 and 2009 in the metropolitan area of Naples and Caserta in southern Italy. Age-standardized m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26425
更新日期:2013-12-01 00:00:00
abstract::Oral squamous cell carcinoma (OSCC), the subtype of head and neck cancers, is notorious for its high incidence and death rate. The role of long non-coding RNAs (lncRNAs) is discovered to be significant for the canceration and cancer progression. Long intergenic non-protein coding RNA 958 (LINC00958) is discovered as a...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1617571
更新日期:2019-01-01 00:00:00
abstract::The molecular regulation of growth and progression of hormone refractory breast and prostate cancers remains challenging. The Division of Cancer Biology, NCI organized a small "think tank" style workshop and invited scientists in relevant areas to assess the state of science on the biology of hormone refractory tumors...
journal_title:Cancer biology & therapy
pub_type:
doi:10.4161/cbt.8.21.9918
更新日期:2009-11-01 00:00:00
abstract::Multiple Myeloma (MM) is a progressive malignancy with poor prognosis, commonly treated by the use of the glucocorticoid Dexamethasone. Myeloma cells resist Dexamethasone induced apoptosis when exposed to IL-6 or IGF-1, both of which are known to activate several signaling cascades. For the first time, we show the act...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.2.621
更新日期:2004-02-01 00:00:00
abstract::The PROfound trial highlights that there is a benefit in testing genes involved in homologous recombination (HR) and forms the rationale for testing in all patients with metastatic, castration-resistant prostate cancer (mCRPC). This trial also demostrates that olaparib improves progression free survival (PFS), objecti...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1809913
更新日期:2020-10-02 00:00:00
abstract::Tumor formation in immunocompetent hosts is believed to be dependent on the ability of tumor cells to evade the immune system, as suggested by the alterations of expression of the major histocompatibility complex (MHC) and related molecules in a number of cancers. Our previous serial analysis of gene expression (SAGE)...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.10.1142
更新日期:2004-10-01 00:00:00