Distinctive clinicopathological associations of amplification of the <i>cortactin</i> gene at 11q13 in head and neck squamous cell carcinomas

Rodrigo, Juan P.; Garcia-Carracedo, Dario; García, L. Solar; Menendez, S.T.; Allonca, Eva; González, M. Victoria; Fresno, M F; Suárez, Carlos

doi:10.1002/path.2462

Cited by 80 publications

(98 citation statements)

References 26 publications

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“…Cortactin is an oncoprotein located on chromosome 11q13 along with cyclin D1, a site that is frequently amplified in HNSCC (44). In accordance with our findings, high tumor CTTN expression has been shown to correlate with increased aggressiveness and poor outcome in many cancers, but most frequently in HNSCC (37,45).…”

Section: Fig 5 Model For Radioresistance Mediated By Cortactin In Hsupporting

confidence: 89%

Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals Human Papillomavirus (HPV)–dependent Regulation of the Activator Protein 1 (AP-1) Pathway

Sepiashvili

Hui

Shi

et al. 2014

Molecular & Cellular Proteomics

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a HPV-positive oropharyngeal carcinoma (OPC) patients have superior outcomes relative to HPV-negative patients, but the underlying mechanisms remain poorly understood. We conducted a proteomic investigation of HPV-positive (n ‫؍‬ 27) and HPV-negative (n ‫؍‬ 26) formalinfixed paraffin-embedded OPC biopsies to acquire insights into the biological pathways that correlate with clinical behavior. Among the 2,633 proteins identified, 174 were differentially abundant. These were enriched for proteins related to cell cycle, DNA replication, apoptosis, and immune response. The differential abundances of cortactin and methylthioadenosine phosphorylase were validated by immunohistochemistry in an independent cohort of 29 OPC samples (p ‫؍‬ 0.023 and p ‫؍‬ 0.009, respectively). An additional 1,124 proteins were independently corroborated through comparison to a published proteomic dataset of OPC. Furthermore, utilizing the Cancer Genome Atlas, we conducted an integrated investigation of OPC, attributing mechanisms underlying differential protein abundances to alterations in mutation, copy number, methylation, and mRNA profiles. A key finding of this integration was the identification of elevated cortactin oncoprotein levels in HPV-negative OPCs. These proteins might contribute to reduced survival in these patients via their established role in radiation resistance. Through interrogation of Cancer Genome Atlas data, we demonstrated that activation of the ␤1-integrin/FAK/cortactin/

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Section: Fig 5 Model For Radioresistance Mediated By Cortactin In Hsupporting

confidence: 89%

Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals Human Papillomavirus (HPV)–dependent Regulation of the Activator Protein 1 (AP-1) Pathway

Sepiashvili

Hui

Shi

et al. 2014

Molecular & Cellular Proteomics

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“…Discussion 11q13 is a frequently amplified chromosomal region in several human cancers with poor prognosis (3-7). Although CCND1 is considered to be the main tumor-promoting gene in this amplicon, it does not have predictive value for the survival of HNSCC and breast cancer patients (8,(11)(12)(13)(14). The 11q13 amplicon harbors several independent amplification cores, indicating the presence of additional driving oncogenes in this region (6,15,16,34).…”

Section: Ano1 Regulates Egfr-and Calcium-dependent Signaling Pathwaysmentioning

confidence: 99%

“…Although cyclin D1 (CCND1) has been considered to be the main driver of the 11q13 amplicon (8)(9)(10), it is not sufficient for malignant transformation of normal breast cells and lacks predictive value for the survival of head-and-neck squamous cell carcinoma (HNSCC) or breast cancer patients (8,(11)(12)(13)(14). Instead, the region has been shown to harbor several independent amplification cores, indicating that other genes could be potential driving oncogenes (6,15,16).…”

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confidence: 99%

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

Britschgi

Bill

Brinkhaus

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

270

373

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The calcium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the most frequently amplified chromosomal regions in human cancer, but its functional role in tumorigenesis has remained unclear. The 11q13 region is amplified in ∼15% of breast cancers. Whether ANO1 is amplified in breast tumors, the extent to which gene amplification contributes to ANO1 overexpression, and whether overexpression of ANO1 is important for tumor maintenance have remained unknown. We have found that ANO1 is amplified and highly expressed in breast cancer cell lines and primary tumors. Amplification of ANO1 correlated with disease grade and poor prognosis. Knockdown of ANO1 in ANO1-amplified breast cancer cell lines and other cancers bearing 11q13 amplification inhibited proliferation, induced apoptosis, and reduced tumor growth in established cancer xenografts. Moreover, ANO1 chloride channel activity was important for cell viability. Mechanistically, ANO1 knockdown or pharmacological inhibition of its chloride-channel activity reduced EGF receptor (EGFR) and calmodulin-dependent protein kinase II (CAMKII) signaling, which subsequently attenuated AKT, v-src sarcoma viral oncogene homolog (SRC), and extracellular signal-regulated kinase (ERK) activation in vitro and in vivo. Our results highlight the involvement of the ANO1 chloride channel in tumor progression and provide insights into oncogenic signaling in human cancers with 11q13 amplification, thereby establishing ANO1 as a promising target for therapy in these highly prevalent tumor types.ion channel | CaCCinh-A01 | TMEM16A | HNSCC | ESCC

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“…An increase of motility and invasiveness was described for HNSCC cell lines with CTTN amplification and cortactin overexpression, which decreased after selective cortactin knock-down (22). Retrospective studies found an association of amplification and adverse patient outcome in HNSCC (23). In this respect, the increase of transcriptional activity on chromosomal bands 3q26.3-qter and 11q12-q13 detected by CESH in our analysis is probably the result of distinct DNA copy number gains in these chromosome regions underlining the validity and reliability of the present experimental approach.…”

Section: Discussionmentioning

confidence: 99%

Comparative expressed sequence hybridization detects recurrent patterns of altered sequence expression in oral squamous cell carcinoma

et al. 2010

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Abstract. Despite its common histology and presentation, oral squamous cell carcinoma (OSCC) is associated with widely varying clinical behaviour and response to therapy. To further elucidate the molecular basis of OSCC, an approach for gene expression analysis termed comparative expressed sequence hybridization (CESH) was used in the present study. This straightforward approach allows the rapid delineation of pathophysiologically interesting candidate chromosome regions by a direct detection of aberrant transcriptional activation. CESH profiling of OSCC specimens led to the identification of several novel chromosomal regions. Increased expression compared to a set of control mucosa specimens was found on 1q22-q23, 3q26.3-qter, 4q31.1-q32, 11q12-q13.2, 14q32, 18q12, 19q13.2-q13.3 and 22q13.1-q13.2. Decreased expression was found on 8p22-p23, 16p12 and 16q23-q24. Using CESH, common patterns of altered sequence expression in different OSCC samples were obtained. While some of these regions overlap with those known to be frequently altered in OSCC on the genomic level, this screen revealed novel chromosome subregions with increased transcriptional activity, which are probably independent of the genomic status of the tumor cells. IntroductionOral squamous cell carcinoma (OSCC) is the 10th most common human malignancy worldwide affecting more than 500000 individuals per year. The 5-year survival rate for oral squamous cell carcinoma does not currently exceed 55%, which is mainly caused by locally aggressive tumor phenotypes and early loco-regional metastases (1). In general, clinicopathological parameters such as the TNM system, which are used as basis for therapeutic decisions, do not adequately predict the biological behaviour of the tumors. To improve the clinical management of individual patients, there is a strong requirement for a better understanding of molecular events involved in OSCC formation. Genetic changes associated with malignant transformation and tumor progression critically affect the expression of key genes. To further elucidate the molecular basis of these critical events, an approach termed comparative expressed sequence hybridization (CESH) was recently introduced in molecular analyses of tumor specimen (2). The principles of CESH are similar to chromosomal comparative genomic hybridization (cCGH), but instead of differently labeled genomic DNA, cDNA sequences derived from cellular RNA are used as hybridization probe for test and control specimen. This allows the analysis of global expression patterns of both coding and non-coding genes in tumor specimens. Since its first publication, the CESH method was established and applied on different subtypes of rhabdomyosarcoma (RMS), Wilms' tumors, hairy cell leukemia, acute lymphoblastic leukemia and breast cancer (3-5). It was shown that individual tumor subtypes within these tumor entities could be distinguished by their expression profiles obtained by CESH. Moreover, combining cCGH and CESH experiments allowed the correlation of chromosome copy num...

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Distinctive clinicopathological associations of amplification of the cortactin gene at 11q13 in head and neck squamous cell carcinomas

Cited by 80 publications

References 26 publications

Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals Human Papillomavirus (HPV)–dependent Regulation of the Activator Protein 1 (AP-1) Pathway

Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals Human Papillomavirus (HPV)–dependent Regulation of the Activator Protein 1 (AP-1) Pathway

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

Comparative expressed sequence hybridization detects recurrent patterns of altered sequence expression in oral squamous cell carcinoma

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