Abstract:
BACKGROUND:Recent advances have revealed a significant contribution of chemokines and their receptors in tumor growth, survival after chemotherapy, and organ-specific metastasis. The CXC chemokine receptor-7 (CXCR7) is the latest chemokine receptor implicated in cancer. Although over expressed in breast cancer cell lines and tumor tissues, its mechanism of action in breast cancer (BrCa) growth and metastasis is unclear. Studies in other cancers have implicated CXCR7 in cell proliferation, anti-apoptotic activity and cell-cell adhesion. The present study was initiated to examine the pattern of CXCR7 expression and its role in regulation of growth signaling in breast cancer. METHODS:The contribution of CXCR7 in BrCa cell proliferation was investigated in representative cell lines using real time quantitative PCR (q-PCR), proliferation assays, immunohistochemistry and immunoblotting. Phenotypic changes were examined after CXCR7 specific cDNA and siRNA transfection and expression levels were monitored by q-PCR. Further, the association of CXCR7 with epidermal growth factor receptor (EGFR) and modulation of its activity were investigated by western blotting, immunofluorescence, and in-situ proximity ligation assays in human BrCa cells and tissues. RESULTS:CXCR7 was expressed in both, estrogen receptor (ER) positive and negative BrCa cell lines. CXCR7 was also expressed unevenly in normal breast tissues and to a much higher extent in ER + cancer tissues. Depletion of CXCR7 in MCF7 BrCa cells by RNA interference decreased proliferation and caused cell cycle arrest. Further, proximity ligation assay (PLA) revealed colocalization of CXCR7 with EGFR in cancer tissues and cancer cell lines. CXCR7 depletion reduced levels of phospho-EGFR at Tyrosine1110 after EGF-stimulation and also reduced phosphorylation of ERK1/2, indicating a potentially direct impact on mitogenic signaling in MCF7 cells. Using siRNA to knockdown β-arrestin2 in cells with EGFR over expression we were able to nearly deplete the CXCR7-EGFR colocalization events, suggesting that β-arrestin2 acts as a scaffold to enhance CXCR7 dependent activation of EGFR after EGF stimulation. CONCLUSIONS:These results demonstrate coupling of CXCR7 with EGFR to regulate proliferation of BrCa cells and suggest an important ligand-independent role of CXCR7 in BrCa growth. Thus, the CXCR7-EGFR axis is a promising target for breast cancer therapy.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Salazar N,Muñoz D,Kallifatidis G,Singh RK,Jordà M,Lokeshwar BLdoi
10.1186/1476-4598-13-198subject
Has Abstractpub_date
2014-08-28 00:00:00pages
198issn
1476-4598pii
1476-4598-13-198journal_volume
13pub_type
杂志文章相关文献
Molecular Cancer文献大全abstract:BACKGROUND:Hedgehog acyltransferase (Hhat) catalyzes the transfer of the fatty acid palmitate onto Sonic Hedgehog (Shh), a modification that is essential for Shh signaling activity. The Shh signaling pathway has been implicated in the progression of breast cancer. METHODS:To determine the functional significance of Hh...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0345-x
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:The dioxin (AhR) receptor can have oncogenic or tumor suppressor activities depending on the phenotype of the target cell. We have shown that AhR knockdown promotes melanoma primary tumorigenesis and lung metastasis in the mouse and that human metastatic melanomas had reduced AhR levels with respect to benig...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0419-9
更新日期:2015-08-05 00:00:00
abstract:BACKGROUND:The disruption of normal gene regulation due to microRNA dysfunction is a common event in cancer pathogenesis. MicroRNA-27b is an example of an oncogenic miRNA, and it is frequently upregulated in breast cancer. MicroRNAs have been found to deregulate tumor metabolism, which typically manifests as heightened...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0851-8
更新日期:2018-07-16 00:00:00
abstract:BACKGROUND:The clinical efficacy of camptothecin (CPT), a drug specifically targeting topoisomerase I (TopoI), is under evaluation for the treatment of malignant gliomas. Due to the high unresponsiveness of these tumours to chemotherapy, it would be very important to study the signalling network that drives camptotheci...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-7-66
更新日期:2008-08-11 00:00:00
abstract:BACKGROUND AND METHODS:Stem or progenitor cells from healthy tissues have the capacity to co-segregate their template DNA strands during mitosis. Here, we set out to test whether breast cancer cell lines also possess the ability to asymmetrically segregate their template DNA strands via non-random chromosome co-segrega...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-139
更新日期:2013-11-15 00:00:00
abstract:BACKGROUND:The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFbeta is a transcriptional co-activator that is ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-171
更新日期:2010-06-30 00:00:00
abstract:BACKGROUND:In recent years, circular RNAs (circRNAs), a new star of non-coding RNA, have been emerged as vital regulators and gained much attention for involvement of initiation and progression of diverse kinds of human diseases, especially cancer. However, regulatory role, clinical significance and underlying mechanis...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0933-7
更新日期:2019-01-08 00:00:00
abstract::Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body's immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects t...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0913-y
更新日期:2018-11-26 00:00:00
abstract::Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC) patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing poten...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-6-73
更新日期:2007-11-17 00:00:00
abstract:BACKGROUND:The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for c...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-020-01165-x
更新日期:2020-02-27 00:00:00
abstract:BACKGROUND:Glycochenodeoxycholate (GCDA) is one of the major human bile salts. Bile salts stimulate cell survival and proliferation through the mitogen-activated protein kinase, but the downstream signaling mechanism(s) remains enigmatic. Mcl-1 is an antiapoptotic molecule of the Bcl2 family that is extensively overexp...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-44
更新日期:2011-04-20 00:00:00
abstract::By nature, scientists contribute to our understanding of nature and ourselves. As communities undergo significant changes, new challenges are presented. Here, we offer alternative views on recent changes in society. ...
journal_title:Molecular cancer
pub_type: 社论
doi:10.1186/1476-4598-7-63
更新日期:2008-07-17 00:00:00
abstract:BACKGROUND:The exposure of skin keratinocytes to Ultraviolet (UV) irradiation leads to Akt phosphorylation at Ser-473, which is important for the carcinogenic effects of excessive sun exposure. The present study investigated the underlying mechanism of Akt Ser-473 phosphorylation by UVB radiation. RESULTS:We found tha...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-172
更新日期:2013-12-24 00:00:00
abstract:BACKGROUND:Though esophageal cancer is three to four times more common among males than females worldwide, this type of cancer still ranks in the top incidence among women, even more than the female specific cancer types. The occurrence is currently attributed to extrinsic factors, including tobacco use and alcohol con...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-019-0949-7
更新日期:2019-02-08 00:00:00
abstract::This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1186/s12943-015-0389-y. ...
journal_title:Molecular cancer
pub_type: 杂志文章,撤回出版物
doi:10.1186/s12943-020-01242-1
更新日期:2020-08-15 00:00:00
abstract:BACKGROUND:Aberrant accumulation of beta-catenin plays an important role in a variety of human neoplasms. We recently reported accumulation of beta-catenin in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). In CTNNB1 exon 3, we detected a stabilizing mutation (S37A) in 3 out of 20 analyzed a...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-7-53
更新日期:2008-06-09 00:00:00
abstract:BACKGROUND:CADM1 encodes an immunoglobulin superfamily (IGSF) cell adhesion molecule. Inactivation of CADM1, either by promoter hypermethylation or loss of heterozygosity, has been reported in a wide variety of tumor types, thus it has been postulated as a tumor suppressor gene. FINDINGS:We show for the first time tha...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-11-29
更新日期:2012-05-03 00:00:00
abstract:BACKGROUND:Cellular senescence is a state of irreversible cell growth arrest and senescence cells permanently lose proliferation potential. Induction of cellular senescence might be a novel therapy for cancer cells. TRIB2 has been reported to participate in regulating proliferation and drug resistance of various cancer...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0922-x
更新日期:2018-12-12 00:00:00
abstract:BACKGROUND:The influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs. METHODS:The demethylation rate of the TSDR (TSDR...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-153
更新日期:2014-06-18 00:00:00
abstract::Methionine aminopeptidase 2 (MetAP2) is a bifunctional protein that plays a critical role in the regulation of post-translational processing and protein synthesis. MetAP2 is overexpressed in human colon cancer. In this report we screened various MetAP2 inhibitors and treated HT29 cells with various concentrations of c...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-65
更新日期:2009-08-24 00:00:00
abstract::Infection with Human papillomaviruses (HPVs) leads to the development of a wide-range of cancers, accounting for 5% of all human cancers. A prominent example is cervical cancer, one of the leading causes of cancer death in women worldwide. It has been well established that tumor development and progression induced by ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-015-0361-x
更新日期:2015-04-17 00:00:00
abstract:BACKGROUND:CD44 is considered as 'a' metastasis associated gene, despite the fact that it is an umbrella term for a group of molecules produced from a single gene by alternative splicing. However, little consideration is given to the above in the literature of colorectal carcinomas as well as other tumour types, leadin...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-11-83
更新日期:2012-11-14 00:00:00
abstract:BACKGROUND:Hypoxia can halt cell cycle progression of several cell types at the G1/S interface. The arrest needs to be overcome by cancer cells. We have previously shown that the hypoxia-inducible cellular oxygen sensor PHD3/EGLN3 enhances hypoxic cell cycle entry at the G1/S boundary. METHODS:We used PHD3 knockdown b...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0410-5
更新日期:2015-07-30 00:00:00
abstract:BACKGROUND:TGF-beta resistance often develops in breast cancer cells that in turn overproduce this cytokine to create a local immunosuppressive environment that fosters tumor growth and exacerbates the invasive and metastatic behavior of the tumor cells themselves. Smads-mediated cross-talk with the estrogen receptor h...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-111
更新日期:2009-11-27 00:00:00
abstract:BACKGROUND:The tetraspanin CD63 is a highly N-glycosylated protein that is known to regulate cancer malignancy. However, the contribution of glycosylation of CD63 to cancer malignancy remains unclear. Previously, we reported that ribophorin II (RPN2), which is part of an N-oligosaccharyle transferase complex, is respon...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-134
更新日期:2014-05-31 00:00:00
abstract:BACKGROUND:Expression of kappa gene is under the control of distinct cis-regulatory elements, including the kappa intron enhancer (iE kappa) and the kappa 3' enhancer (3'E kappa). The active enhancers and expression of immunoglobulin is generally considered to be restricted to B lymphocytes. However, accumulating evide...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-92
更新日期:2009-10-27 00:00:00
abstract:BACKGROUND:Patients with colorectal cancer (CRC) have a high incidence of regional and distant metastases. Although metastasis is the main cause of CRC-related death, its molecular mechanisms remain largely unknown. METHODS:Using array-CGH and expression microarray analyses, changes in DNA copy number and mRNA express...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0853-6
更新日期:2018-07-23 00:00:00
abstract:BACKGROUND:The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0435-9
更新日期:2015-09-24 00:00:00
abstract::Circular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across species ranging from viruses to mammals. Important advances have been made in the biogenesis, regulation, localization, degradation and modification of circRNAs. CircRNAs exert biological functions by acting as tra...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-020-01286-3
更新日期:2020-12-14 00:00:00
abstract:BACKGROUND:The AKT/mammalian target of rapamycin (mTOR) signaling pathway is regulated by 17α-estradiol (E2) signaling and mediates E2-induced proliferation and progesterone receptor (PgR) expression in breast cancer. METHODS AND RESULTS:Here we use deep sequencing analysis of previously published data from The Cancer...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-229
更新日期:2014-10-06 00:00:00