MYC regulation of a "poor-prognosis" metastatic cancer cell state.

نویسندگان

  • Anita Wolfer
  • Ben S Wittner
  • Daniel Irimia
  • Richard J Flavin
  • Mathieu Lupien
  • Ruwanthi N Gunawardane
  • Clifford A Meyer
  • Eric S Lightcap
  • Pablo Tamayo
  • Jill P Mesirov
  • X Shirley Liu
  • Toshi Shioda
  • Mehmet Toner
  • Massimo Loda
  • Myles Brown
  • Joan S Brugge
  • Sridhar Ramaswamy
چکیده

Gene expression signatures are used in the clinic as prognostic tools to determine the risk of individual patients with localized breast tumors developing distant metastasis. We lack a clear understanding, however, of whether these correlative biomarkers link to a common biological network that regulates metastasis. We find that the c-MYC oncoprotein coordinately regulates the expression of 13 different "poor-outcome" cancer signatures. In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits distant metastasis in vivo and invasive behavior in vitro of these cells. These results suggest that MYC oncogene activity (as marked by "poor-prognosis" signature expression) may be necessary for the translocation of poor-outcome human breast tumors to distant sites.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Evaluation of HER2, MDM2, MYC, MET and TP53 gene copy number alterations in gastric cancer patients

Background: Gastric cancer (GC) is considered as one of the most common types of cancer worldwide with poor prognosis and generally limited treatment options. Recent studies have indicated that HER2, MDM2, MYC, MET, and TP53 play an important role in the development of gastric cancer. Therefore, the aim of this study was to evaluate the incidence of amplification/deletion of these genes in pati...

متن کامل

N-myc Downstream Regulated Gene 1 (NDRG1) Promotes Metastasis of Human Scirrhous Gastric Cancer Cells through Epithelial Mesenchymal Transition

Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 u...

متن کامل

Molecular Biology, Pathobiology, and Genetics Inhibition of Rho-Associated Kinase Signaling Prevents Breast Cancer Metastasis to Human Bone

Rho-associated kinase (ROCK) signaling plays a fundamental role in regulating cell morphology, adhesion, and motility. Aberrant expression of ROCK is related to tumor metastases and poor clinical outcome. Here, we show that ROCK expression is increased in metastatic human mammary tumors and breast cancer cell lines compared with nonmetastatic tumors and cell lines. Overexpression of ROCK confer...

متن کامل

HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition

BACKGROUND Homeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined. METHODS Immunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prog...

متن کامل

Increased Cytotoxicity of Cisplatin in SK-MEL 28 Melanoma Cells upon Down-Regulation of Melanoma Inhibitor of Apoptosis Protein

Background: Malignant melanoma is a highly metastatic cutaneous cancer and typically refractory to chemotherapy. Deregulated apoptosis has been identified as a major cause of cancer drug resistance, and upregulated expression of the inhibitor of apoptosis protein melanom, an inhibitor of apoptosis (ML-IAP) is frequent in melanoma. Methods: Based on the conclusion that ML-IAP expression contribu...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 107 8  شماره 

صفحات  -

تاریخ انتشار 2010