Membrane Molecules Help Drive Cancer Metastases

MedicalResearch.com Interview with:

Dr Stéphanie Kermorgant PhD
Barts Cancer Institute
Queen Mary University of London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is an urgent need to better understand how cancer spreads around the body (a process called metastasis). Often it is metastasis that kills cancer patients and not the primary tumour.

During metastasis, cancer cells detach from the primary tumour and are able to survive detached, allowing them to enter in blood vessels and colonize different parts of the body.

Integrins and growth factor receptors are two classes of cell surface molecules that have been known to cooperate to promote cancer metastasis. However how they communicate is poorly understood. They have mostly been shown to exert their function at the surface of the cells.

Our study reveals that one growth factor receptor, called c-Met, and one integrin, beta1-integrin, in fact communicate inside the cancer cell to increase its survival when detached.

Moreover, this communication occurs in an anusual place in the cell, that we have called “Autophagy Related Endomembrane” (ARE). Autophagy is normally a process that degrades and recycles cellular material, making new building blocks for the cell. Our study reveals that intracellular structures related to the autophagy process can also help membrane receptors to communicate. Thus they may also function as “signalling platforms”.

One other key finding in this study is that integrins normally have been recognized to function as “adhesion molecules”, connecting the cells to their surrounding environment, the “extracellular matrix”. Their role in metastasis has been mostly linked to their adhesive function. Our exciting study reveals a new function of integrins, a “signalling function”, which is independent from their adhesion function.

MedicalResearch.com: What should readers take away from your report?

Response: Membrane receptors do not signal from the cell surface only, as found in textbooks, but enter in the cells and signal from there.

We may need to reconsider the function of integrins as adhesive molecules only. We may take in account they also are signalling molecules, inside the cells, independently from their adhesive property.

Intracellular membrane structures, part of the autophagy process, may help membrane receptor signalling, increasing cancer cell survival and metastasis.

Our study was performed in human breast and lung cancer cells cultured in vitro or grafted in mice or zebrafish embryos to analyze metastasis in vivo. Integrins and growth factor receptors such as c-Met represent attractive targets for cancer therapy and inhibitors already exist but success in the clinic is limited.

Our results may have implication for the design of novel, different, cancer therapies.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Improving the knowledge of how membrane receptors enter and signal inside the cancer cells may provide novel strategies to reduce metastasis.

A better understanding of how integrins play a “signalling” role independent form their “adhesive” role will help design new therapy to fully alter the function of integrins. It is hoped this knowledge will provide more effective treatment to slow cancer spread and improve patient outcome

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Barrow-McGee, R. et al. Beta 1-integrin–c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes.

Nat. Commun. 7:11942 doi: 10.1038/ncomms11942 (2016).

FUNDER
UK Medical Research Council, Breast Cancer Now, Rosetrees Trust, British Lung Foundation, Cancer Research UK and Barts Charity

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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