Integrin Survival Mechanism Revealed in Cancer Metastasis
Author: Queen Mary University of London
Published: 2016/06/24 - Updated: 2025/12/09
Publication Details: Peer-Reviewed, Research, Study, Analysis
Category Topic: Cancer - Tumors - Related Publications
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research, published in the peer-reviewed journal Nature Communications by scientists at Queen Mary University of London, reveals a previously unknown survival mechanism that cancer cells use during metastasis - the deadly process by which tumors spread throughout the body. The findings demonstrate how integrin proteins switch from their known adhesive function to an entirely new form of internal cellular communication called "inside-in" signaling, partnering with another protein (c-Met) to help detached cancer cells resist death as they travel through the body.
What makes this work particularly valuable is that it addresses metastasis, which remains largely incurable and represents the actual cause of death in most cancer patients rather than primary tumors themselves. The practical implications extend to patients across all demographics, including older adults and people with disabilities who face cancer diagnoses, as the research points toward more effective drug targets that could prevent the formation of secondary tumors - something current integrin-blocking medications have struggled to accomplish because they only target surface adhesion rather than this newly discovered internal signaling pathway - Disabled World (DW).
Introduction
Cancer cells appear to depend on an unusual survival mechanism to spread around the body, according to an early study led by Queen Mary University of London (QMUL). The discovery could help with future development of novel treatments to prevent metastasis and secondary tumors.
The spread of cancer around the body - metastasis - is one of the biggest challenges in cancer treatment. It is often not the original tumor that kills, but secondary growths. These happen when cancer cells are able to break away from the primary site, travel around the body and 'seed' new tumor's.
Main Content
A key question in cancer research has been how cancer cells are able to survive once they break away from a tumor to spread around the body? Cells are relatively protected when they are attached to other cancer cells and their surroundings, but become more vulnerable when they detach and 'float', and normally undergo cell death.
Lead researcher Dr Stéphanie Kermorgant from QMUL's Barts Cancer Institute said:
"Metastasis is currently incurable and remains one of the key targets of cancer research. Our research advances the knowledge of how two key molecules communicate and work together to help cancer cells survive during metastasis. We're hoping that this might lead to the discovery of new drugs to block the spread of cancer within the body."
The study, published in Nature Communications, examined the changes that occur in cancer cells as they break away from tumor's in cell cultures, zebrafish and mice. The researchers revealed a previously unknown survival mechanism in cancer cells and found that molecules known as 'integrins' could be key.
Integrins are proteins on the cell surface that attach to and interact with the cell's surroundings. 'Outside-in' and 'inside-out' signaling by integrins is known to help the cancer cells attach themselves to their surroundings. But the study suggests that when the cancer cells are floating, as they do during metastasis, the integrins switch from their adhesion role to take on an entirely new form of communication which has never been seen before - 'inside-in' signaling, in which integrins signal within the cell.
The researchers discovered that an integrin called beta-1 (β1) pairs up with another protein called c-Met and they move inside the cell together. The two proteins then travel to an unexpected location within the cell which is normally used to degrade and recycle cell material. Instead the location is used for a new role of cell communication and the two proteins send a message to the rest of the cell to resist against death while floating during metastasis.
Using both breast and lung cells, the team found that metastases were less likely to form when β1 and c-Met were blocked from entering the cell together or were prevented from moving to the special location within the cell.
Integrins are already major targets for cancer treatment with drugs either being tested or in use in the clinic. Most integrin inhibitor drugs target their adhesive function and block them on the surface of the cancer cell. The researchers say that the limited success of these drugs could be partly explained by this newly discovered role of integrins within the cancer cell.
A new strategy could be to prevent the integrin from going inside the cell in the first place. The researchers hope that these insights could lead to the design of better therapies against metastasis and more effective treatment combinations that could prevent and slow both tumor growth and spread.
About the Research
The research was funded by the UK Medical Research Council, Breast Cancer Now, Rosetrees Trust, British Lung Foundation, Cancer Research UK and Barts Charity.
The team carried out part of their animal research work on zebrafish embryos in order to implement the principle of 3Rs (refine, reduce, replace) on their research on mice. Zebrafish provide a similar tumor microenvironment to humans, meaning fewer tests need to be carried out in mice and any future experiments in mice will have been optimized to have minimal toxicity. They are aiming to reduce the number of mice used by at least 90 percent and ultimately use zebrafish to completely replace the use of mice.
Research paper: Barrow-McGee, R. et al. Beta 1-integrin-c-Met cooperation reveals an inside-in survival signaling on autophagy related endomembranes. Nature Communications 7:11942 (2016)
Insights, Analysis, and Developments
Editorial Note: The elegance of this discovery lies not just in identifying a new cellular mechanism, but in explaining why existing treatments have fallen short. By revealing that integrins essentially lead double lives - one on the cell surface and another hidden within - these findings challenge a decade of drug development assumptions and suggest that we've been aiming at only half the target. The implications reach beyond laboratory curiosity into genuine clinical promise: if researchers can develop compounds that prevent integrins from entering cells or block their internal partnership with c-Met, they might finally crack the metastasis problem that has eluded oncologists for generations. Perhaps most encouraging is the team's commitment to refining their research methods through zebrafish models, demonstrating that scientific progress need not come at the expense of animal welfare - a consideration that matters deeply when the ultimate goal is reducing suffering in all its forms - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Queen Mary University of London and published on 2016/06/24, this content may have been edited for style, clarity, or brevity.