Nav: Home

Important signaling pathway in breast cancer revealed

January 24, 2019

In breast cancer, one of the most common cancers in women, tumors contain a small amount of so-called cancer stem-like cells (CSCs). Being able to eliminate breast-cancer stem-like cells in a targeted way is essential for developing successful therapies -- conventional treatments, such as chemotherapy or radiotherapy followed by drug intake, do not target CSCs. A better understanding of the processes generating CSCs in breast-cancer tumors is needed. Noriko Gotoh from Kanazawa University and colleagues have now uncovered a signaling pathway directly related to the proliferation of CSCs in breast cancer.

A property of stem cells is that they can self-renew and differentiate. Two types of stem-cell division can occur: symmetric or asymmetric (Fig. 1). In the former, two self-renewing stem cells are generated; in the latter, only one (and a differentiated cell). It is now believed that malignant CSCs have a higher tendency to divide symmetrically, thus increasing the number of CSCs. Gotoh and colleagues looked at how the microenvironment of CSCs, called the CSC niche, causes and sustains an increased rate of symmetric division.

The researchers started from the observation that a particular gene encoding a type of cytokine known as Semaphorin 3 (Sema3) was one of the most-expressed genes in the CSC niche (Fig. 2). (Cytokines are small proteins that, when released, affect the behavior of cells around them.) The production of Sema3 activates another protein, called MICAL3, the expression levels of which were also found to be high in the CSC niche.

Via a series of experiments in vitro, Gotoh and colleagues were able to confirm the critical roles of Sema3 and MICAL3 in breast cancer tumor development. Specifically, MICAL3 was shown to be required for tumor sphere formation (tumorigenicity is associated with spherical cell shapes). The scientists showed that Sema3-stimulated MICAL3 triggered a whole sequence of biomolecular interactions (a signaling pathway), ultimately resulting in induced symmetric division of CSCs, and hence their proliferation, in breast cancer (Fig. 3).

Having established this important pathway is highly relevant for developing treatments for breast cancer, because, quoting Gotoh and colleagues, "by inhibition of MICAL3 ... or knockdown of each component in the signaling pathway, the symmetric cell division may be inhibited, leading to a reduction of breast-cancer stem-like cells."
-end-


Kanazawa University

Related Breast Cancer Articles:

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.
Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.
Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.
Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.
Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
More Breast Cancer News and Breast Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.