Breast cancer growth signals are enhanced by a protein outside cells

July 6, 2018, Rockefeller University Press
Estrogen receptor α (ERα) positive (red) and the fibronectin-binding protein β1-integrin (green) are found together inside cells in tumors (right) but not in healthy breast tissue (left). Credit: Sampayo et al., 2018

New research uncovers how a sticky protein called fibronectin promotes the activity of estrogen in breast cancer cells. The study, "Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells," which will be published July 6 in the Journal of Cell Biology (JCB), was led by Rocío Sampayo, a Ph.D. student in Dr. Marina Simian's lab at the Instituto de Nanosistemas, Universidad Nacional de San Martin and Instituto "Ángel H. Roffo," Universidad de Buenos Aires in Argentina. Together they show a novel mechanism of estrogen receptor signaling that is regulated by fibronectin. They found that exposure to fibronectin prolongs the activity of estrogen receptors in breast cancer cells.

The hormone estrogen plays a key role in the development of healthy and, in many cases, cancerous cells. Estrogen attaches to cellular estrogen receptors, which promote cell growth and survival. But too much activity can cause cells to proliferate rapidly, leading to tumor growth. About 75% of breast cancers are considered estrogen receptor positive because estrogen causes those cancers to propagate, Sampayo notes.

As cancerous cells start to invade into surrounding tissue, they encounter the gluey fibronectin protein. "In the normal mammary gland, epithelial cells are not in contact with fibronectin," Sampayo explains. Fibronectin is part of the extracellular matrix, the meshwork of proteins and molecules that surrounds cells. In tumors, the production of this surrounding network often becomes unregulated. Previous research has shown that high levels of fibronectin and its receptor β1-integrin correlate with lower breast survival, but it was not known why.

In the current study, Sampayo and colleagues discovered that fibronectin boosts estrogen receptors' activity in . They found that when breast cancer cells are surrounded by fibronectin, estrogen receptors avoid destruction by lysosomes—cellular garbage disposal units—and can continue to drive cancer cell growth. "This would allow breast cancer cells to become resistant to common endocrine therapy drugs that target the receptor," Sampayo says.

Their research suggests that therapeutics that interfere with fibronectin's influence on the receptor could help treat drug-resistant breast cancers. This work also reveals how the meshwork of proteins surrounding tumors can influence cancer progression.

Explore further: Researchers identify potential therapeutic target in aggressive breast cancer cells

More information: Sampayo et al., 2018. J. Cell Biol. DOI: 10.1083/jcb.201703037

Related Stories

Researchers identify potential therapeutic target in aggressive breast cancer cells

November 15, 2017
An especially aggressive breast cancer cell can respond to hormone therapy if they express a specific protein known as estrogen receptor beta (ERβ), according to new research published on the cover of Oncotarget. The findings ...

New insights into mechanisms of breast cancer development and resistance to therapy

January 9, 2017
Why does breast cancer develop and how come certain patients are resistant to established therapies? Researchers from the University of Basel have gained new insights into the molecular processes in breast tissue. They identified ...

Novel therapeutic target discovered for estrogen receptor positive (ER+) breast cancer

November 17, 2017
Researchers at the Icahn School of Medicine at Mount Sinai have identified a protein that can be targeted to suppress growth of a common type of breast cancer known as "estrogen receptor positive" (ER+), including ER+ cancers ...

Exposure to BPA substitute, BPS, multiplies breast cancer cells

April 2, 2017
Bisphenol S (BPS), a substitute for the chemical bisphenol A (BPA) in the plastic industry, shows the potential for increasing the aggressiveness of breast cancer through its behavior as an endocrine-disrupting chemical, ...

Possible new weapon found for fighting some types of breast cancer

June 23, 2014
Researchers believe they have discovered one reason why some women with estrogen receptor-positive breast cancer may respond poorly or only temporarily to estrogen-blocking drugs such as tamoxifen. Results of a new study, ...

Recommended for you

First immunotherapy success for triple-negative breast cancer

October 21, 2018
There is new hope for people with an aggressive type of breast cancer, as an immunotherapy trial shows for the first time that lives can be extended in people with triple-negative breast cancer.

Healthy diets linked to better outcomes in colorectal cancer

October 20, 2018
Colorectal cancer patients who followed healthy diets had a lower risk of death from colorectal cancer and all causes, even those who improved their diets after being diagnosed, according to a new American Cancer Society ...

Why some cancers affect only young women

October 19, 2018
Among several forms of pancreatic cancer, one of them specifically affects women, often young. How is this possible, even though the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, known ...

Scientists to improve cancer treatment effectiveness

October 19, 2018
Together with researchers from the University of Nantes and the University of Reims Champagne-Ardenne in France, experts from the National Research Nuclear University MEPhI have recently developed a quantum dot-based microarray ...

Mutant cells colonize our tissues over our lifetime

October 18, 2018
By the time we reach middle age, more than half of the oesophagus in healthy people has been taken over by cells carrying mutations in cancer genes, scientists have uncovered. By studying normal oesophagus tissue, scientists ...

Study involving hundreds of patient samples may reveal new treatment options of leukemia

October 17, 2018
After more than five years and 672 patient samples, an OHSU research team has published the largest cancer dataset of its kind for a form of leukemia. The study, "Functional Genomic Landscape of Acute Myeloid Leukemia", published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.