Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

05 Mar 2017 - 09 Mar 2017
20 Mar 2017 - 23 Mar 2017
12 Apr 2017 - 14 Apr 2017

Hypoxia-inducible Transcription Factors Trigger Metastasis in Malignant Melanoma Tumors

By BiotechDaily International staff writers
Posted on 06 May 2013
ADVERTISEMENT
SARTORIUS AG
Cancer researchers have linked the hypoxia-inducible transcription factors HIF1 and HIF2 to the processes that control metastasis in melanoma tumors.

Hypoxia-inducible factors (HIFs) are transcription factors that respond to changes in available oxygen in the cellular environment, specifically, to decreases in oxygen, or hypoxia. HIFs promote the activation of genes involved in cancer initiation, progression, and metastases. Hypoxia has been shown to enhance the invasiveness and metastatic potential of tumor cells by regulating the genes involved in the breakdown of the ECM (extracellular matrix) as well as genes that control motility and adhesion of tumor cells. HIF activity is upregulated by mutated RAS, a member of the KRAS family of oncogenes, and BRAF (v-raf murine sarcoma viral oncogene homolog B1) as well as loss-of-function mutations of the PTEN gene. PTEN (phosphatase and tensin homolog), which is missing in 60% to 70% of metastatic cancers in humans, is the name of a phospholipid phosphatase protein, and gene that encodes it. The PTEN gene acts as a tumor suppressor gene thanks to the role of its protein product in regulation of the cycle of cell division, preventing cells from growing and dividing too rapidly.

Investigators at the University of North Carolina (Chapel Hill, USA) examined the molecular basis for melanoma metastasis in a genetically engineered PTEN-deficient, BRAF-mutant mouse model. In this model the activities of HIF1 and HIF2, which are usually overexpressed in melanoma tumors, can be shut down.

Results published in the April 8, 2013, online edition of the Journal of Clinical Investigation revealed that inactivation of HIF1 or HIF2 prevented metastasis without affecting primary tumor formation. Both HIF1 and HIF2 independently activated the proto-oncogene tyrosine-protein kinase SRC (v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)) using different signaling pathways.

The protein encoded by the SRC gene has been linked to several different cancers, and the identification of its role in melanoma may mean that existing drugs that target SRC may be adapted for treatment of malignant melanoma.

“What we are trying to do now is inhibit these pathways with drugs in the mice to see if we see a decrease of metastasis,” said first author Sara Hanna, a graduate student researcher at the University of North Carolina.

Related Links:

University of North Carolina




Channels

Drug Discovery

view channel
Image: The experimental drug NGI-1 slows cancer growth by blocking glycosylation of the epidermal growth factor receptor (EGFR), which is shown in the above diagram (Photo courtesy of Wikimedia Commons).

Experimental Drug Slows Lung Cancer Growth by Blocking Protein Glycosylation

An interesting new experimental anti-cancer drug slows growth of certain lung tumor cells by preventing the glycosylation of critical cell surface receptor proteins. Asparagine (N)-linked glycosylation... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.