Breast cancer is not a patent of women, although it is more than 100 times common in women than in men, and males tend to have poorer outcomes due to delays in diagnosis.To offer information and support to those affected by breast cancer, Breast Cancer Awareness Month (BCAM) was founded in 1985. BCAM is an annual international health campaign organized by major breast cancer charities every October to increase awareness of the disease and to raise funds for research into its cause, prevention, diagnosis, treatment and cure. As well as providing a platform for breast cancer charities to raise awareness of their work and of the disease, BCAM is also a prime opportunity to remind women to be breast aware for earlier detection. Now, the pink ribbon has become the international symbol of breast cancer awareness.
Worldwide, more than 20% of all cancers in women are breast cancers. Even in some of the historical art paintings, such as the “Portrait of a young woman” (Raffaelo Sanzio), the indications of visible evidence of breast cancer could also be seen. But breast cancer is not the most terrifying monster due to its relatively optimistic outcomes, according to a recent survey, in England, more than 80% women diagnosed of breast cancer survived it for at least 5 years.
Base on different schemes and criteria, breast cancer could be classified into several categories, and different cancer type has individualized symptoms, treatments and survival rates. Among them, the ER/PR/HER2 triple negative breast cancer is the one with the worst outcomes. So far, no effective target medicines are available to anti-triple negative breast cancer, nor it is sensitive to radia- or chemo-therapies. So, till now, its possible treatment target is still the saving taste waiting for grabbing.
For responding this challenge, Dr. CHEN Ceshi’s group (Kunming Institute of Zoology, the CAS) have conducted series research to reveal the pathology mechanisms of triple negative breast cancer. According to their earlier results, a transcription factorkrüppel-like factor 5 (KLF5), which promotes breast cell proliferation partially through a downstream gene, fibroblast growth factor binding protein 1 (FGF-BP), is highly expressing in triple negative breast cancers. And the WWP1 E3 ubiquitine ligase is capable to accelerate the KLF5 protein degradation and then suppress its function.
To discover the up-regulation pathway opposites the known down-regulation pathway, the postdoctoral fellow ZHAO Dong and his colleagues (KIZ, the CAS) have carried out both in vitro cell line experiments and in vivo mice experiments. The results show that the transcriptional co-activator with a PDZ-binding motif (TAZ) interacted with the KLF5 protein through the WW domain and PY motif, specifically attenuated the WWP1-, but not Fbw7-, mediated KLF5 degradation, and increased the KLF5 activities of inducing FGFBP gene expression and promoting breast cell proliferation. Their findings suggest that TAZ, as the key effector of the Hippo tumor suppressor pathway, promotes breast cell growth partially through stabilizing KLF5. KLF5 and TAZ are potential therapeutic targets in a subset of ER-negative breast cancers.
The main findings of this research have been published on Carcinogenesis (http://carcin.oxfordjournals.org/content/early/2011/10/31/carcin.bgr242.short).
