Category Archives: Articles

Publication: CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

Thomas R. Cox, Aug 2019

CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

We are super excited to announce that our recent work in close collaboration with A/Prof Paul Timpson has just been published in Nature Communications (view the full Open-Access article here)

In this work (which was a large international collaboration), co-led by our team and Paul Timpson’s team (also at the Garvan Institute), we show that remodeling of the stromal  tissue in and around pancreatic tumours may be the key to stopping their spread and improving chemotherapy outcomes.

Cancer cell CAF crosstalk

What we did

We already know that tumours are made up of heterogenous populations of cancer cells with different mutational landscapes. Furthermore, recently, the field has begun to realise that the cancer associated fibroblasts (CAFs) present in and around the tumour are also a diverse collection of  subpopulations.

Continue reading

Publication: The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Thomas R. Cox, Aug 2019

The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Just published in Cancer Reports is our new protocol paper detailing the development of a rapid high-throughput (96wp) 3D organotypic coculture assay that is optimised for screening cancer cell and cancer-associated fibroblast response to drugs in physiologically relevant matrices.

Mini-Organo workflow

Continue reading

Publication: LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity

Thomas R. Cox, May 2019

LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity

Our lab has contributed to a recent paper by Zeltz and colleagues looking at the interplay between Lysyl Oxidase Like 1 (LOXL1) and Integrin α11 in Non-Small Cell Lung Cancer (NSCLC). The work was published in the Open-Access journal Cancers.

LOXL1, integrin a11 and ECM crosstalk

Continue reading

Publication: Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

Thomas R. Cox, May 2019

Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

A new paper has just been published revealing the role of Lysyl Oxidase Like 2 (LOXL2) in the remodelling of the prostate cancer microenvironment. The work, carried out in collaboration with lead researchers from the Cancer Program, Biomedicine Discovery Institute at Monash University has just been published in Molecular and Cellular Proteomics.

Normal Prostate Fibroblast and Cancer Associated Fibroblast proteomics

Continue reading

Publication: Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

Thomas R. Cox, Mar 2019

Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

We have just published a new paper in Breast Cancer Research in collaboration with lead researcher Dr. David Croucher from the Garvan Institute, looking at how and why ERBB2 (HER2) positive breast cancer cells develop resistance to targeted therapies such as trastuzumab (Herceptin™).

Promiscuity of the ERBB2 receptor in breast cancer

Continue reading

Publication: The extracellular matrix as a key regulator of intracellular signalling networks

Thomas R. Cox, Jan 2019

The extracellular matrix as a key regulator of intracellular signalling networks

Our latest review in collaboration with Dr. David Croucher  and Dr. Dirk Fey on ‘The extracellular matrix as a key regulator of intracellular signalling networks‘ has just been published as part of a special series on ‘Translating the Matrix’ in the British Journal of Pharmacology.

Extracellular matrix interplay with MAPK-JNK Signalling

Computational model of the interplay between the ECM and drug activated MAPK‐JNK signalling network.

At their simplest, cells follow a set of rules governed by their genetic code. These rules, which are executed by the protein‐based signalling networks that the genes encode, control the assimilation of information and decision‐making processes that shape a cell’s response to their surroundings.

Continue reading

Publication: Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

Thomas R. Cox, Oct 2018

Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

Just published in Molecular Biology of the Cell is our recent paper looking at the effect of extracellular matrix stiffness on the intrinsic biomechanical properties of cancer cells. Led by Professors Janine Erler (Biotech Research & Innovation Centre) and Lene Oddershede (Niels Bohr Institute) both from the University of Copenhagen, the study combines optical tweezers–based microrheology and deformability cytometry with 3D biological models to dissect how cancer cells biomechanically interact with and respond to the stiffness of the microenvironment they are within.

Optical Tweezers Schematic for measuring intracellular viscosity

Optical Tweezers Schematic for measuring intracellular viscosity

The results show that invasive cancer cells adjust their intracellular and overall viscoelasticity to ECM density, and that cancer cell viscosity increases during invasion into 3D collagen matrices.

Continue reading

Publication: Tumor endothelial marker 8 promotes cancer progression and metastasis

Thomas R. Cox, Jul 2018

Tumor endothelial marker 8 promotes cancer progression and metastasis

Our new paper has just been published in Oncotarget. In this study, we show that Tumor endothelial marker 8 (TEM8) regulates the expression of multiple genes. In particular, we observed that the most common expression changes conserved between breast and colorectal cancer are involved in regulation of the cell cycle. In line with the microarray results we show that TEM8 regulates cancer cell proliferation and primary tumor growth. Since TEM8 KO tumors presented with fewer blood vessels we hypothesize that TEM8 contributes to the regulation of angiogenesis, likely by being secreted by cancer cells to alter endothelial cell migration and thereby supporting growth of the tumor. Moreover, we confirm that TEM8 is an important player in driving tumor cell invasion and metastatic dissemination in breast cancer.

Tumor endothelial marker 8 promotes cancer progression and metastasis

Proposed mechanism behind the impact of TEM8 on breast and CRC cancer progression.

Continue reading

Publication: Removing physiological motion from intravital and clinical functional imaging data

Thomas R. Cox, Jul 2018

Removing physiological motion from intravital and clinical functional imaging data

Galene is a new tool just published in eLife that can correct for physiological motion in live imaging data post-acquisition.

Galene Motion Correction Software

eLife digest

Understanding how molecules and cells behave in living animals can give researchers key insights into what goes wrong in diseases such as cancer, and how well potential treatments for these diseases work. Continue reading