Genes and pathways downstream of telomerase in melanoma metastasis.

نویسندگان

  • Sepideh Bagheri
  • Mehdi Nosrati
  • Shang Li
  • Sylvia Fong
  • Sima Torabian
  • Javier Rangel
  • Dan H Moore
  • Scot Federman
  • Rebecca R Laposa
  • Frederick L Baehner
  • Richard W Sagebiel
  • James E Cleaver
  • Christopher Haqq
  • Robert J Debs
  • Elizabeth H Blackburn
  • Mohammed Kashani-Sabet
چکیده

Recent studies have demonstrated a role for telomerase in driving tumor progression, but its mechanism of action remains unclear. Here we show that stable, ribozyme-mediated suppression of mouse telomerase RNA reduced telomerase RNA expression, telomerase activity, and telomere length, which significantly reduced tumor invasion and metastatic potential. Our studies reveal that previously unidentified effects of telomerase may mediate its tumor-promoting effects. First, reducing telomerase activity induced a more dendritic morphology, accompanied by increased melanin content and increased expression of tyrosinase, a key enzyme in melanin biosynthesis. Second, gene expression profiling revealed that telomerase targeting down-regulated expression of several glycolytic pathway genes, with a corresponding decrease in glucose consumption and lactate production. Thus, telomerase activity controls the glycolytic pathway, potentially altering the energy state of tumor cells and thereby modulating tyrosinase activity and melanin production. These studies have important implications for understanding the mechanisms by which telomerase promotes tumor invasion and metastasis.

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

The role of microRNA-30a and downstream snail1 on the growth and metastasis of melanoma tumor

Objective(s): Growing evidences have indicated microRNAs as modulators of tumor development and aggression. On the other hand, a phenomenon known as epithelial-mesenchymal transition (EMT) that indicates a transient phase from epithelial-like features to mesenchymal phenotype is a key player in tumor progression.  In this study, we aimed to assess the potential impacts...

متن کامل

Identification of key genes in melanoma metastasis and investigating their potential as biomarkers

Background and Aim: Considering the high global incidence of skin cancer and the high mortality rate caused by melanoma, it is important to identify the genes involved in this disease and predict effective drugs. Therefore, in this study, we have identified and investigated the expression level of effective and key genes in melanoma metastasis, as well as investigating their diagnostic potentia...

متن کامل

Identification of key genes and pathways involved in vitiligo vulgaris by gene network analysis

Background and Aim: Vitiligo vulgaris is an acquired, chronic skin and hair condition characterized clinically by loss of melanin, which, if untreated, is typically progressive and irreversible. The aim of the present study was to identify potential genes involved in the pathogenesis of vitiligo. Methods: One dataset of mRNA expression in patients with vitiligo (GSE65127) were obtained from ...

متن کامل

Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line

Objective(s): Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. Materials an...

متن کامل

بررسی بیان شاخص‌های سطحی CD133، CD44 و ABCG2 در رده‌های سلولی ملانوما و ارتباط آنها با سلول‌های بنیادی سرطان

 Background and Objective: Melanoma is the most deadly type of skin cancer that has a high potency and rapid metastasis to other organs. It appears that cancer stem cells (CSCs) are responsible for invasion and metastasis. The aim of this study was to investigate the expression of cancer stem cells candidate markers and their association with stemness features in mel...

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 103 30  شماره 

صفحات  -

تاریخ انتشار 2006