We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us

Download Mobile App




Gene Therapy Prevents Cancer Cells from Surviving in Hypoxic Environment

By Gerald M. Slutzky, PhD
Posted on 08 Dec 2016
Gene therapy techniques were used to insert a peptide into cultures of human cancer cells that blocked their ability to use the enzyme Hypoxia-inducible factor-1, a heterodimeric transcription factor that enables cell survival under low oxygen conditions by altering the transcription of over 300 genes.

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival, and progression of tumors. More...
There is significant evidence that inhibition of HIF-1 would be beneficial for cancer therapy, since tumor cells must thrive in a microenvironment characterized by lack of oxygen. In previous work, investigators at the University of Southampton (United Kingdom) discovered a cyclic hexapeptide (cyclo-CLLFVY) that inhibited the HIF-1alpha/HIF-1beta protein–protein interaction in vitro and prevented HIF-1-mediated hypoxia-response signaling in cells. This cyclic peptide was identified by screening a library that contained more than 3.2 million compounds.

With a view to demonstrating the potential for encoding the production of a therapeutic agent in response to a disease marker, the investigators engineered human cells with an additional chromosomal control circuit that conditionally encoded the production of the cyclic peptide HIF-1 inhibitor. They then demonstrated the conditional production of the HIF-1 inhibitor in response to hypoxia, and its inhibitory effect on HIF-1 dimerization and downstream hypoxia-response signaling.

Results published in the November 23, 2016, online edition of the journal ACS Synthetic Biology revealed that the engineered cells demonstrated the synthetic lethality of inhibiting HIF-1 dimerization and glycolysis in hypoxic cells. This approach not only eliminated the need for the chemical synthesis and targeted delivery of the HIF-1 inhibitor to cells; it also demonstrated the wider possibility that the production machinery of other bioactive compounds may be incorporated onto the chromosome of human cells.

Senior author Dr. Ali Tavassoli, professor of chemical biology at the University of Southampton, said, "We have been able to show that the engineered cells produce the HIF-1 inhibitor, and this molecule goes on to inhibit HIF-1 function in cells, limiting the ability of these cells to survive and grow in a nutrient-limited environment as expected. In a wider sense, we have given these engineered cells the ability to fight back - to stop a key protein from functioning in cancer cells. This opens up the possibility for the production and use of sentinel circuits, which produce other bioactive compounds in response to environmental or cellular changes, to target a range of diseases including cancer."

"Dr. Tavassoli said, "The main application for this work is that it eliminates the need for the synthesis of our inhibitor, so that biologists conducting research into HIF function can easily access our molecule and hopefully discover more about the role of HIF-1 in cancer. This will also let us understand whether inhibiting HIF-1 function alone is enough to block cancer growth in relevant models. Another interesting aspect to the work is that it demonstrates the possibility of adding new machinery to human cells to enable them to make therapeutic agents in response to disease signals."

Related Links:
University of Southampton


Gold Member
Quality Control Material
iPLEX Pro Exome QC Panel
Portable Electronic Pipette
Mini 96
New
ESR Analyzer
TEST1 2.0
New
Sample Transportation System
Tempus1800 Necto
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Clinical Chemistry

view channel
Image: The study highlights the potential of cCAFs as a biomarker for early diagnosis and prognosis (H J Woo et al., Analytical Chemistry (2025). DOI: 10.1021/acs.analchem.5c02154)

Simultaneous Cell Isolation Technology Improves Cancer Diagnostic Accuracy

Accurate cancer diagnosis remains a challenge, as liquid biopsy techniques often fail to capture the complexity of tumor biology. Traditional systems for isolating circulating tumor cells (CTCs) vary in... Read more

Hematology

view channel
Image: New research points to protecting blood during radiation therapy (Photo courtesy of 123RF)

Pioneering Model Measures Radiation Exposure in Blood for Precise Cancer Treatments

Scientists have long focused on protecting organs near tumors during radiotherapy, but blood — a vital, circulating tissue — has largely been excluded from dose calculations. Each blood cell passing through... Read more

Immunology

view channel
Image: The VENTANA HER2 (4B5) test is now CE-IVDR approved (Photo courtesy of Roche)

Companion Diagnostic Test Identifies HER2-Ultralow Breast Cancer and Biliary Tract Cancer Patients

Breast cancer is the most common cancer in Europe, with more than 564,000 new cases and 145,000 deaths annually. Metastatic breast cancer is rising in younger populations and remains the leading cause... Read more

Technology

view channel
Image: Conceptual design of the CORAL capsule for microbial sampling in the small intestine (H. Mohammed et al., Device (2025). DOI: 10.1016/j.device.2025.100904)

Coral-Inspired Capsule Samples Hidden Bacteria from Small Intestine

The gut microbiome has been linked to conditions ranging from immune disorders to mental health, yet conventional stool tests often fail to capture bacterial populations in the small intestine.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.