Nav: Home

Tumor suppressor APC could stop cancer through its effect on actin cytoskeleton

June 21, 2010

The APC protein serves as the colon's guardian, keeping tumors at bay. Now researchers reveal a new function for the protein: helping to renovate the cytoskeleton by triggering actin assembly. The result suggests a second way that mutations in APC could lead to cancer. The study appears online on June 21 in the Journal of Cell Biology (www.jcb.org).

A faulty APC gene occurs in more than 80% of colon cancers and is one of the early "gateway" mutations leading to abnormal growth. Researchers probing APC's anti-cancer powers have focused on how it curbs the activity of beta-catenin, a key link in the Wnt pathway that manages cell division and differentiation. But APC also helps shape the cytoskeleton. The protein latches onto and stabilizes growing microtubule ends and connects to actin filaments, though it was unclear exactly how APC affects actin dynamics.

A team of researchers led by Bruce Goode at Brandeis University found that APC plays matchmaker, corralling actin monomers into a complex that seeds further elongation. But that discovery raised another question. Cells deploy proteins that rein in actin extension. For example, profilin latches onto actin monomers and curbs spontaneous nucleation. And capping protein seals the barbed ends of actin filaments, preventing them from elongating and thus limiting their growth. APC can assemble actin filaments even if profilin is around. But how does it overcome capping protein?

The answer is that APC gets help, collaborating with formins that deter capping protein. The team found that when capping protein and profilin are present, APC or the formin mDia1 alone is a weak nucleator. But combining the two boosts actin assembly nearly fourfold.

APC is the seventh actin nucleator that researchers have identified. "The cellular functions of actin are so pervasive," Goode says. "It's involved in dozens of critical processes, so it makes sense that cells have a large number of factors that promote actin assembly." So far, APC is the only nucleator with direct links to cancer. Goode says that it's plausible that APC mutations could foment tumors not just through their effects on Wnt signaling, but also through their impact on the cytoskeleton, because cancer-causing mutations typically lop off the protein's actin-binding section.
-end-
About The Journal of Cell Biology

Founded in 1955, The Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jcb.org.

Okada, K., et al 2010. J. Cell Biol. doi:10.1083/jcb.201001016.

Rockefeller University Press

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...