HIF1-alpha expressing cells induce a hypoxic-like response in neighbouring cancer cells

Hannah Harrison, Henry J Pegg, Jamie Thompson, Christian Bates, Paul Shore

Preprint posted on March 18, 2018

Article now published in BMC Cancer at

A new hypoxic-inducible system reveals non-localised effects of oxygen deprivation

Selected by Anh Hoang Le

What did the authors discover?

Studying hypoxia in cell culture systems has been frequently speculated to not reflect the natural heterogeneity within a tumour. This is because cultured cells are usually exposed to a homogenous condition to induce hypoxia in all of them. This is far from reality since, within a tumour, hypoxic regions are scattered randomly. Thus the way we used to study hypoxia can lead to loss of information that may well be vital to understanding the biology of tumours.

To overcome this, the authors have created an HIF1-inducible system based on the fact that the transcription factor Hypoxia-inducible factor 1 (HIF1) is one of the main response routes the cell uses to cope with hypoxic stress.  They attached a destabilising domain to HIF1 and upon the addition of a chemical called TMP, the HIF1-fusion protein is stabilised. By forcing the cell to express HIF1,  conditions of low oxygen are mimicked. Since this engineered protein is stable, induced cells can be mixed with non-induced cells, and this allows the authors to study a more heterogeneous population, recreating the kind of environment found inside a real tumour.

A surprising finding is that HIF1-expressing cells – in this case, two breast cancer cell lines – somehow influence surrounding cells; they even change the gene expression patterns of these cells, similar to what hypoxia would cause.


What I found interesting

I personally think the system is rather simple but elegant. This allows us to better model a more physiologically relevant system in a petri dish, which is highly accessible compared to systems like intravital imaging.  As shown by the authors, a heterogeneous environment of cells can easily be mimicked, and we can learn a lot just from this simple technique.


Unanswered questions

Nevertheless, there are a few questions that need to be answered. Thinking of complex biological systems, hypoxia is an intricate response by cells; thus, only expressing one protein may not be reflecting the entire hypoxic response mechanism.

Crosstalk between cells is a common mechanism cancer cells use to communicate. What mediates this paracrine signalling pathway between hypoxic cells and non-hypoxic cells? One interesting hypothesis is that this occurs through exosomes. Exosomes are vesicular structures released by cells, including cancer cells. It has been shown that hypoxia can increase the release of these vesicles [1]. However, what components are carried with them that cause cells to react in a certain way is largely unknown. By using this system, we may just be able to take a closer look at this.

[1] King, WM. (2012) Hypoxic enhancement of exosome release by breast cancer cell. BMC Cancer, 12:421 DOI: 10.1186/1471-2407-12-421

Tags: cancer model, heterogenous, hif1, hypoxia, intratumoural

Posted on: 12th April 2018

Read preprint (No Ratings Yet)

  • Have your say

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cell biology category:

    3D Gastruloids

    A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells)


    List by Paul Gerald L. Sanchez and Stefano Vianello

    ECFG15 – Fungal biology

    Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome


    List by Hiral Shah

    ASCB EMBO Annual Meeting 2019

    A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)


    List by Madhuja Samaddar, Ramona Jühlen, Amanda Haage, Laura McCormick, Maiko Kitaoka

    EMBL Seeing is Believing – Imaging the Molecular Processes of Life

    Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019


    List by Gautam Dey


    Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.


    List by Sandra Malmgren Hill

    Lung Disease and Regeneration

    This preprint list compiles highlights from the field of lung biology.


    List by Rob Hynds

    Cellular metabolism

    A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.


    List by Pablo Ranea Robles

    BSCB/BSDB Annual Meeting 2019

    Preprints presented at the BSCB/BSDB Annual Meeting 2019


    List by Gautam Dey


    This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.


    List by Sandra Franco Iborra

    ASCB/EMBO Annual Meeting 2018

    This list relates to preprints that were discussed at the recent ASCB conference.


    List by Gautam Dey, Amanda Haage