Focal overexpression of CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis

Cameron, Sarina; Long, Lilia Merida de; Hazar-Rethinam, Mehlika; Topkas, Eleni; Endo‐Munoz, Liliana; Cumming, A.; Gannon, Orla M.; Guminski, Alexander; Saunders, Nicholas A.

doi:10.1186/1476-4598-11-74

Cited by 28 publications

(19 citation statements)

References 30 publications

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“…CEACAM6 is known to be oncogenic, as it inhibits cell differentiation and anoikis, causes the loss of cell polarity, and promotes cell adhesion, invasion, and metastasis [15][16][17][18]. The role of CEACAM6 in adhesion, invasion, and metastasis can be inhibited by the fragment of antigen binding (Fab 0 ) of an anti-CEACAM6 antibody in breast, pancreatic, and colorectal cancers [19], and our in vitro results were in line with these reports.…”

Section: Discussionsupporting

confidence: 82%

CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer

Zhang¹,

Zang²,

Li³

et al. 2014

ABBS

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Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) shows increased expression in a wide variety of human cancers, and its over-expression is associated with enhanced migration, invasion, and in vivo metastasis. Here, we reported that CEACAM6 was up-regulated in gastric cancer (GC) cell lines and tumor tissues. Overexpression of CEACAM6 in MKN-45 and SGC-7901 GC cells promoted migration and invasion in vitro and metastasis in athymic mice, whereas migration and invasion of MKN-28 and SNU-16 GC cells were suppressed by knockdown of CEACAM6. We also observed that steroid receptor coactivator (C-SRC) phosphorylation was increased when CEACAM6 was over-expressed in SGC-7901 cells. Taken together, these results suggested that CEACAM6 functions as an oncoprotein in GC and may be an important metastatic biomarker and therapeutic target.

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Section: Discussionsupporting

confidence: 82%

CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer

Zhang¹,

Zang²,

Li³

et al. 2014

ABBS

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“…As such, these cells contribute to the replenishment of the epithelial cell layer. We further propose that CEACAM6 is both a marker of these progenitor cells and a contributor to the proliferative response by virtue of its antiapoptotic and cell adhesive properties (Ordonez et al 2000;Cameron et al 2012;Han et al 2014).…”

Section: Discussionmentioning

confidence: 95%

Expression of Carcinoembryonic Cell Adhesion Molecule 6 and Alveolar Epithelial Cell Markers in Lungs of Human Infants with Chronic Lung Disease

Gonzales

Gonzalez

Barrette

et al. 2015

J Histochem Cytochem.

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The membrane protein carcinoembryonic antigen cell adhesion molecule (CEACAM6) is expressed in the epithelium of various tissues, participating in innate immune defense, cell proliferation and differentiation, with overexpression in gastrointestinal tract, pancreatic and lung tumors. It is developmentally and hormonally regulated in fetal human lung, with an apparent increased production in preterm infants with respiratory failure. To further examine the expression and cell localization of CEACAM6, we performed immunohistochemical and biochemical studies in lung specimens from infants with and without chronic lung disease. CEACAM6 protein and mRNA were increased ~4-fold in lungs from infants with chronic lung disease as compared with controls. By immunostaining, CEACAM6 expression was markedly increased in the lung parenchyma of infants and children with a variety of chronic lung disorders, localizing to hyperplastic epithelial cells with a ~7-fold elevated proliferative rate by PCNA staining. Some of these cells also co-expressed membrane markers of both type I and type II cells, which is not observed in normal postnatal lung, suggesting they are transitional epithelial cells. We suggest that CEACAM6 is both a marker of lung epithelial progenitor cells and a contributor to the proliferative response after injury due to its anti-apoptotic and cell adhesive properties.

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“…Whilst there are no published studies on the existence of genetically distinct clonal variants within a single OS lesion, the presence of intra-tumoural heterogeneity within OS is inferred by the varied responses of patient lesions to chemotherapy. In contrast, there is definitive proof of genetically distinct clonal variants within many common cancer types [ 6 , 40 , 41 ] which have been shown to drive phenotypic variability with respect to drug resistance or tumour initiating activity. In the present study, we demonstrate that clonal variants exist within an established human OS cell line and differ in their transcriptomes as well as in their ability to metastasise in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Little is known about the factors that drive metastatic progression in OS, however in a number of cancers, intratumoural heterogeneity has been shown to give rise to phenotypic variants within a single tumour that contribute to chemotherapeutic resistance or metastases [ 3 – 6 ]. In this study, we exploited inherent differences in metastatic potential of clonal variants isolated from the same parental cell line to identify potential drivers of OS metastasis.…”

Section: Introductionmentioning

confidence: 99%

Auranofin is a potent suppressor of osteosarcoma metastasis

et al. 2015

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Osteosarcoma (OS) accounts for 56% of malignant bone cancers in children and adolescents. Patients with localized disease rarely develop metastasis; however, pulmonary metastasis occurs in approximately 50% of patients and leads to a 5-year survival rate of only 10–20%. Therefore, identifying the genes and pathways involved in metastasis, as new therapeutic targets, is crucial to improve long-term survival of OS patients. Novel markers that define metastatic OS were identified using comparative transcriptomic analyses of two highly metastatic (C1 and C6) and two poorly metastatic clonal variants (C4 and C5) isolated from the metastatic OS cell line, KHOS. Using this approach, we determined that the metastatic phenotype correlated with overexpression of thioredoxin reductase 2 (TXNRD2) or vascular endothelial growth factor (VEGF). Validation in patient biopsies confirmed TXNRD2 and VEGF targets were highly expressed in 29–42% of metastatic OS patient biopsies, with no detectable expression in non-malignant bone or samples from OS patients with localised disease. Auranofin (AF) was used to selectively target and inhibit thioredoxin reductase (TrxR). At low doses, AF was able to inhibit TrxR activity without a significant effect on cell viability whereas at higher doses, AF could induce ROS-dependent apoptosis. AF treatment, in vivo, significantly reduced the development of pulmonary metastasis and we provide evidence that this effect may be due to an AF-dependent increase in cellular ROS. Thus, TXNRD2 may represent a novel druggable target that could be deployed to reduce the development of fatal pulmonary metastases in patients with OS.

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Focal overexpression of CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis

Cited by 28 publications

References 30 publications

CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer

CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer

Expression of Carcinoembryonic Cell Adhesion Molecule 6 and Alveolar Epithelial Cell Markers in Lungs of Human Infants with Chronic Lung Disease

Auranofin is a potent suppressor of osteosarcoma metastasis

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