Menu

Close

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 https://www.biorxiv.org/content/early/2018/03/18/266213

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 *

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

    Register here

    Also in the biochemistry category:

    Site-specific K63 ubiquitinomics reveals post-initiation regulation of ribosomes under oxidative stress

    Songhee Back, Christine Vogel, Gustavo M Silva



    Selected by Srivats Venkataramanan

    1

    Template switching causes artificial junction formation and false identification of circular RNAs

    Chong Tang, Tian Yu, Yeming Xie, et al.



    Selected by Fabio Liberante

    Dynamics and interactions of ADP/ATP transporter AAC3 in DPC detergent are not functionally relevant

    Vilius Kurauskas, Audrey Hessel, François Dehez, et al.

    AND

    Major concerns with the integrity of the mitochondrial ADP/ATP carrier in dodecyl-phosphocholine used for solution NMR studies

    Martin S. King, Paul G. Crichton, Jonathan J. Ruprecht, et al.



    Selected by Reid Alderson

    1

    Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin

    Kwo-Kwang Abraham Wang, Tai L. Ng, Peng Wang, et al.



    Selected by Ellis O'Neill

    TTL proteins scaffold brassinosteroid signaling components at the plasma membrane to optimize signal transduction in plant cells

    Vitor Amorim-Silva, Alvaro Garcia-Moreno, Araceli G Castillo, et al.



    Selected by Martin Balcerowicz

    1

    OptoGranules reveal the evolution of stress granules to ALS-FTD pathology

    Peipei Zhang, Baochang Fan, Peiguo Yang, et al.



    Selected by Srivats Venkataramanan

    1

    Structural Basis of Tubulin Recruitment and Assembly by Tumor Overexpressed Gene (TOG) domain array Microtubule Polymerases

    Stanley Nithiananatham, Brian Cook, Fred Chang, et al.

    AND

    Roles for tubulin recruitment and self-organization by TOG domain arrays in Microtubule plus-end tracking and polymerase

    Brian Cook, Fred Chang, Ignacio Flor-Parra, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    A robust method for transfection in choanoflagellates illuminates their cell biology and the ancestry of animal septins

    David Booth, Heather Middleton, Nicole King



    Selected by Maya Emmons-Bell

    SWI/SNF remains localized to chromatin in the presence of SCHLAP1

    Jesse R Raab, Keriayn N Smith, Camarie C Spear, et al.



    Selected by Carmen Adriaens

    1

    A non-canonical role for dynamin-1 in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells

    Saipraveen Srinivasan, Christoph J. Burckhardt, Madhura Bhave, et al.



    Selected by Penelope La-Borde

    Higher-Order Organization Principles of Pre-translational mRNPs

    Mihir Metkar, Hakan Ozadam, Bryan R. Lajoie, et al.



    Selected by Carmen Adriaens

    Capturing the onset of PRC2-mediated repressive domain formation

    Ozgur Oksuz, Varun Narendra, Chul-Hwan Lee, et al.



    Selected by Boyan Bonev

    RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs

    Mark A McClintock, Carly I Dix, Christopher M Johnson, et al.

    AND

    Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex

    Thomas E. Sladewski, Neil Billington, M. Yusuf Ali, et al.



    Selected by Dmitry Nashchekin

    Dynamic Kinetochore Size Regulation Promotes Microtubule Capture And Chromosome Biorientation In Mitosis

    Carlos Sacristan, Misbha Ahmad, Jenny Keller, et al.

    AND

    Self-assembly of the RZZ complex into filaments drives kinetochore expansion in the absence of microtubule attachment

    Cláudia Pereira, Rita M Reis, José B Gama, et al.



    Selected by Gautam Dey

    Directed evolution of TurboID for efficient proximity labeling in living cells and organisms

    Tess C Branon, Justin A Bosch, Ariana D Sanchez, et al.



    Selected by Ralph Böttcher

    Nuclear envelope assembly defects link mitotic errors to chromothripsis

    Shiwei Liu, Mijung Kwon, Mark Mannino, et al.



    Selected by Gautam Dey

    Also in the cancer biology category:

    Memory sequencing reveals heritable single cell gene expression programs associated with distinct cellular behaviors

    Sydney M Shaffer, Benjamin L Emert, Ann E. Sizemore, et al.



    Selected by Leighton Daigh

    1

    Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling

    Amber N Stratman, Olivia M Farrelly, Constantinos M Mikelis, et al.



    Selected by Coert Margadant

    Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling

    Junnian Wei, Kevin K. Leung, Charles Truillet, et al.



    Selected by Rob Hynds

    1

    Precise tuning of gene expression output levels in mammalian cells

    Yale S. Michaels, Mike B Barnkob, Hector Barbosa, et al.



    Selected by Tim Fessenden

    1

    Moving beyond P values: Everyday data analysis with estimation plots

    Joses Ho, Tayfun Tumkaya, Sameer Aryal, et al.



    Selected by Gautam Dey

    1

    JNK-mediated spindle reorientation in stem cells promotes dysplasia in the aging intestine

    Daniel Hu, Heinrich Jasper



    Selected by Maiko Kitaoka

    Mitotic chromosome alignment is required for proper nuclear envelope reassembly

    Cindy L Fonseca, Heidi LH Malaby, Leslie A Sepaniac, et al.



    Selected by Maiko Kitaoka

    SWI/SNF remains localized to chromatin in the presence of SCHLAP1

    Jesse R Raab, Keriayn N Smith, Camarie C Spear, et al.



    Selected by Carmen Adriaens

    1

    Single-cell Map of Diverse Immune Phenotypes Driven by the Tumor Microenvironment

    Elham Azizi, Ambrose J. Carr, George Plitas, et al.



    Selected by Tim Fessenden

    Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)

    Scott J Callahan, Stephanie Tepan, Yan M Zhang, et al.



    Selected by Hannah Brunsdon

    1

    PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery

    Nathalie Conte, Jeremy Mason, Csaba Halmagyi, et al.



    Selected by Carmen Adriaens

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

    Hannah Harrison, Henry J Pegg, Jamie Thompson, et al.



    Selected by Anh Hoang Le

    Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of cell division, differentiation, and loss

    Judy Martin, Erin Nicole Sanders, Paola Moreno-Roman, et al.



    Selected by Natalie Dye

    A role for RNA and DNA:RNA hybrids in the modulation of DNA repair by homologous recombination

    Giuseppina D'Alessandro, Marek Adamowicz, Donna Whelan, et al.



    Selected by Carmen Adriaens

    Nuclear envelope assembly defects link mitotic errors to chromothripsis

    Shiwei Liu, Mijung Kwon, Mark Mannino, et al.



    Selected by Gautam Dey

    Zebrafish as a model to investigate the effects of exercise in cancer

    Alexandra Yin, Nathaniel R. Campbell, Lee W. Jones, et al.



    Selected by Jacky G. Goetz

    Also in the cell biology category:

    SABER enables highly multiplexed and amplified detection of DNA and RNA in cells and tissues

    Jocelyn Y. Kishi, Brian J. Beliveau, Sylvain W. Lapan, et al.



    Selected by Yen-Chung Chen

    PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection

    Catherine M Buckley, Victoria L Heath, Aurelie Gueho, et al.



    Selected by Giuliana Clemente

    1

    Memory sequencing reveals heritable single cell gene expression programs associated with distinct cellular behaviors

    Sydney M Shaffer, Benjamin L Emert, Ann E. Sizemore, et al.



    Selected by Leighton Daigh

    1

    Aurora A depletion reveals centrosome-independent polarization mechanism in C. elegans

    Kerstin Klinkert, Nicolas Levernier, Peter Gross, et al.

    AND

    Centrosome Aurora A gradient ensures a single PAR-2 polarity axis by regulating RhoGEF ECT-2 localization in C. elegans embryos

    Sachin Kotak, Sukriti Kapoor



    Selected by Giuliana Clemente

    Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling

    Amber N Stratman, Olivia M Farrelly, Constantinos M Mikelis, et al.



    Selected by Coert Margadant

    Neural crest cells regulate optic cup morphogenesis by promoting extracellular matrix assembly

    Chase Dallas Bryan, Rebecca Lynne Pfeiffer, Bryan William Jones, et al.



    Selected by Ashrifia Adomako-Ankomah

    1

    mRNA localisation in endothelial cells regulates blood vessel sprouting

    Guilherme Costa, Nawseen Tarannum, Shane Herbert



    Selected by Andreas van Impel

    Local protein synthesis in axon terminals and dendritic spines differentiates plasticity contexts

    Anne-Sophie Hafner, Paul Donlin-Asp, Beulah Leitch, et al.



    Selected by Dipen Rajgor

    The cytoskeleton as a smart composite material: A unified pathway linking microtubules, myosin-II filaments and integrin adhesions

    Nisha Mohd Rafiq, Yukako Nishimura, Sergey V. Plotnikov, et al.



    Selected by Coert Margadant

    Quantitative, real-time, single cell analysis in tissue reveals expression dynamics of neurogenesis

    Cerys S Manning, Veronica Biga, James Boyd, et al.



    Selected by Teresa Rayon

    Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling

    Junnian Wei, Kevin K. Leung, Charles Truillet, et al.



    Selected by Rob Hynds

    1

    Optogenetic dissection of mitotic spindle positioning in vivo

    Lars-Eric Fielmich, Ruben Schmidt, Daniel J Dickinson, et al.



    Selected by Angika Basant

    1

    Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.

    Jonathan B Michaux, Francois B Robin, William M McFadden, et al.



    Selected by Sundar Naganathan

    Moving beyond P values: Everyday data analysis with estimation plots

    Joses Ho, Tayfun Tumkaya, Sameer Aryal, et al.



    Selected by Gautam Dey

    1

    A limited number of double-strand DNA breaks are sufficient to delay cell cycle progression.

    Jeroen van den Berg, Anna G. Manjon, Karoline Kielbassa, et al.



    Selected by Leighton Daigh

    Optogenetic manipulation of medullary neurons in the locust optic lobe

    Hongxia Wang, Richard B. Dewell, Markus U. Ehrengruber, et al.



    Selected by Ana Patricia Ramos
    Close