I am very excited to announce our new review paper which is out now in Front Cell Dev Biol [Link]. This is also the first paper from Dr Kamila Marzec who recently joined the lab. Great work!
MASTL kinase is a master regulator of mitosis, essential for ensuring that mitotic substrate phosphorylation is correctly maintained. It achieves this through the phosphorylation of alpha-endosulfine and subsequent inhibition of the tumour suppressor PP2A-B55 phosphatase. In recent years MASTL has also emerged as a novel oncogenic kinase that is upregulated in a number of cancer types, correlating with chromosome instability and poor patient survival. While the chromosome instability is likely directly linked to MASTL’s control of mitotic phosphorylation, several new studies indicated that MASTL has additional effects outside of mitosis and beyond regulation of PP2A-B55. These include control of normal DNA replication timing, and regulation of AKT/mTOR and Wnt/β-catenin oncogenic kinase signalling. In this review, we will examine the phenotypes and mechanisms for how MASTL, ENSA and PP2A-B55 deregulation drives tumour progression and metastasis. Finally, we will explore the rationale for the future development of MASTL inhibitors as new cancer therapeutics.
Great news, we have had a co-author review published in the Journal of Molecular and Cellular Biology.
You can check out the full review here.
The major cause of death from breast cancer is not the primary tumour, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defense against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute (MDM) family: comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery. Proper function of the MDM family is vital for normal breast development, but also for preserving genomic fidelity. The MDM family members are best characterized for their negative regulation of the major tumour suppressor p53 to modulate stress responses. Their impact on other cellular regulators is emerging. Inappropriately elevated protein levels of the MDM family are highly associated with an increased risk of cancer incidence. Exploration of the MDM family members as cancer therapeutic targets is relevant for designing tailored anti-cancer treatments, but successful approaches must strategically consider the impact on both the target cancer and adjacent healthy cells and tissues. This review focuses on recent findings pertaining to the role of the MDM family in normal and malignant breast cells.
Great news, Cell Division Lab and Dr Andrew Burgess will be presenting a Poster of some of our latest research at the 29th International Association for Breast Cancer Research Conference (#IABCR14). The conference will be held from the 14 – 17 September 2014 at The Novotel Sydney Manly, New South Wales, and has an amazing line up of world class speakers, is is sure to be an excellent conference.
Rachael’s Paper is now on-line [Link]
Role of endoplasmic reticulum stress induction by the plant toxin, persin, in overcoming resistance to the apoptotic effects of tamoxifen in human breast cancer cells
“The cytotoxic effects of persin are CASP-4 dependent and mediated by CHOP-dependent and -independent ERS signalling cascades. Increased ERS signalling contributes to persin-induced reversal of tamoxifen resistance.”
In simple terms, Persin a toxin from avocados, helps reverse tamoxifen resistance in breast cancer cell lines. Tamoxifen is a critical front line chemotherapeutic drug which has been instrumental in improving the survival rates for women with breast cancer. Future trials are needed to confirm that this result translates to the to humans and then the clinic, but never the less it is still an exciting finding, and a proof of principal that tamoxifen resistance can be reversed.