Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach

Desouki, Mohamed Mokhtar; Liao, Shaoxi; Huang, Huayi; Conroy, Jeffrey M.; Nowak, Norma J.; Shepherd, Lori; Gaile, Daniel P.; Geradts, Joseph

doi:10.1007/s00432-010-0937-1

Cited by 23 publications

(21 citation statements)

References 54 publications

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“…This did not identify any tumor types with recurrent chromosomal losses involving the SCCRO3 locus at 16p12.3 (32)(33)(34). The absence of chromosomal losses at 16p12.3 was validated by our analysis of results from array comparative genomic hybridization and/or single-nucleotide polymorphism investigations performed on thyroid, head and neck, lung, and neuroendocrine tumors at our institution (data not shown).…”

Section: Sccro3 Expression Is Decreased In Human Tumors-wementioning

confidence: 59%

SCCRO3 (DCUN1D3) Antagonizes the Neddylation and Oncogenic Activity of SCCRO (DCUN1D1)

Huang

Stock

Bommeljé

et al. 2014

Journal of Biological Chemistry

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Background: SCCRO3/DCUN1D3 is proposed to function as a tumor suppressor. However, the mechanisms are not well defined. Results: SCCRO3 inhibits SCCRO-promoted nuclear translocation and neddylation of cullins by sequestering them to the cell membrane. Conclusion: SCCRO3 putatively functions as a tumor suppressor by antagonizing the activity of SCCRO. Significance: Understanding how SCCRO and its family members cooperatively regulate cullin neddylation is important for neddylation-targeted cancer therapy.

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Section: Sccro3 Expression Is Decreased In Human Tumors-wementioning

confidence: 59%

SCCRO3 (DCUN1D3) Antagonizes the Neddylation and Oncogenic Activity of SCCRO (DCUN1D1)

Huang

Stock

Bommeljé

et al. 2014

Journal of Biological Chemistry

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“…We find TSPAN1 expression in prostate cancer is biphasic, with upregulation at the primary site and downregulation in metastatic lesions. Similarly, a study in breast cancer has shown that although TSPAN1 is upregulated in most primary tumours it is more likely to be downregulated in metastatic lesions 72 .…”

Section: Discussionmentioning

confidence: 94%

The cancer-associated cell migration protein TSPAN1 is under control of androgens and its upregulation increases prostate cancer cell migration

Munkley

McClurg

Livermore

et al. 2017

Sci Rep

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Cell migration drives cell invasion and metastatic progression in prostate cancer and is a major cause of mortality and morbidity. However the mechanisms driving cell migration in prostate cancer patients are not fully understood. We previously identified the cancer-associated cell migration protein Tetraspanin 1 (TSPAN1) as a clinically relevant androgen regulated target in prostate cancer. Here we find that TSPAN1 is acutely induced by androgens, and is significantly upregulated in prostate cancer relative to both normal prostate tissue and benign prostate hyperplasia (BPH). We also show for the first time, that TSPAN1 expression in prostate cancer cells controls the expression of key proteins involved in cell migration. Stable upregulation of TSPAN1 in both DU145 and PC3 cells significantly increased cell migration and induced the expression of the mesenchymal markers SLUG and ARF6. Our data suggest TSPAN1 is an androgen-driven contributor to cell survival and motility in prostate cancer.Cancer, in its most aggressive form, is not only a disease of uncontrolled cell growth, but also a disease of inappropriate cell migration. Activating invasion and metastasis is a hallmark of cancer progression 1, 2 and is the leading cause of mortality among cancer patients 3 . Metastasis involves cancer cells detaching from the primary tumour, and travelling as circulating tumour cells through the bloodstream or lymphatic system to other parts of the body. Prostate cancer is the most common male cancer in Europe, with around 50,000 new cases in the UK each year 4 . At initial diagnosis 37-43% of men have late stage disease and 17-34% of prostate cancer patients have metastasis (http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ prostate-cancer/incidence#ref-8). The development of prostate cancer is initially driven by androgen steroid hormones via the androgen receptor (AR) transcription factor. The first line treatment for prostate cancer that is no longer organ confined is androgen deprivation therapy (ADT). However, after 2-3 years many patients develop

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“…A few studies have shown that primary tumors and their metastases generally share similar copy number aberrations (12,13) and gene expression profiles (14,15), but these studies were underpowered by the scarcity of metastatic biopsies, limiting the identification of differences between these matched tumor pairs. By using experimental mouse models and a limited series of clinical metastatic biopsies, genes associated with the propensity of breast cancer relapse to the bone (16), lung (17,18), and brain (19) have been published.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

Kimbung

Johansson

Danielsson

et al. 2016

Clinical Cancer Research

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in collaboration with the TEX study group Abstract Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis.Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n ¼ 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested.Results: Liver relapse was associated with estrogen receptor (ER) expression (P ¼ 0.002), luminal B subtype (P ¼ 0.01), and was prognostic for an inferior postrelapse survival (P ¼ 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P ¼ 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P ¼ 0.001) among luminal A tumors.Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer.

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Identification of metastasis-associated breast cancer genes using a high-resolution whole genome profiling approach

Abstract: Metastasizing tumors had a higher rate of deletions, suggesting possible inactivation of metastasis suppressor genes. We provide preliminary evidence that TSPAN1 may be another important breast cancer suppressor gene belonging to the tetraspanin superfamily.

Cited by 23 publications

References 54 publications

SCCRO3 (DCUN1D3) Antagonizes the Neddylation and Oncogenic Activity of SCCRO (DCUN1D1)

SCCRO3 (DCUN1D3) Antagonizes the Neddylation and Oncogenic Activity of SCCRO (DCUN1D1)

The cancer-associated cell migration protein TSPAN1 is under control of androgens and its upregulation increases prostate cancer cell migration

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

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