Thwarting tumour invasion


A mechanism used by metastasising tumour cells to invade lung tissue and establish secondary tumours. The research identifies a promising drug target to prevent the spread of cancer.

Primary tumours prepare the lung for invasion by inducing chemokines – chemical factors normally used to recruit immune cells during infection – which guide migration of tumour cells to the secondary site. Hiratsuka and colleagues show that primary tumours also induce lung cells to produce an additional factor, serum amyloid A3 (SAA3). SAA3 accelerates the recruitment of primary tumour cells by switching on genes involved in inflammation and boosting the production of chemokines. Importantly, the team show that blocking SAA3 or its receptor strikingly reduces lung metastasis in mice.

Metastasis is difficult to predict and even harder to treat. The new findings offer researchers vital clues for understanding how cancer cells can establish new tumours at sites quite distant from the original tumour.

Author contact:
Yoshiro Maru (Tokyo Women's Medical University School of Medicine, Japan)
Tel: +81 3 5269 7417; E-mail: ymaru@research.twmu.ac.jp

Stem-cell regeneration of the breast relies on adhesion


Interaction of basal stem cells in the breast with their cellular environment is crucial for their function, and helps towards the regeneration of the mammary glands during pregnancy, reports a paper online this week in Nature Cell Biology.

The basal stem cells of the breast are enriched in proteins called integrins that mediate contact with the extracellular matrix surrounding the cells. Marina Glukhova and colleagues show that expression of beta 1 integrin in the basal cells is essential for the regenerative potential of these stem cells and for proper development of the mammary gland during pregnancy.

Deletion of the beta 1 integrin gene from the basal layer of mouse mammary tissue led to an abnormal ductal branching pattern in the mammary gland during pregnancy, which results in the regenerative potential of the mammary tissue stem cells being abolished, leading to a dysfunctional gland. In basal stem cells lacking beta 1 integrin, cells divide abnormally and this results in the altered branching pattern.

The environment that surrounds most stem cells, the stem cell niche, is known to be important for a number of stem cells. However, our understanding of stem cell niches remains patchy. These findings establish a central role of direct interaction between basal stem cells and their extracellular matrix in the maintenance of the mammary stem-cell population.

Author contact:
Marina Glukhova (CNRS-Institut Curie Research, Paris, France)
Tel: +33 1 42 34 63 33; E-mail: Marina.Glukhova@curie.fr

p53 hampers energy metabolism in cancer cells


The tumour suppressor p53 can limit tumour development by inhibiting aerobic glycolysis reports a paper.

Cancer cells normally shift their metabolism to aerobic glycolysis - the conversion of glucose to lactic acid in the presence of oxygen - which confers an advantage in sustaining tumour growth.

p53 activity is lost in over half of human tumours; its primary role is to eliminate cells that have undergone oncogenic transformation by inducing cell growth arrest or programmed cell death. Nobuyuki Tanaka and colleagues found, by looking at p53-deficient primary fibroblasts, that loss of p53 leads to higher glucose metabolism, and demonstrated that this requires de-repression of the transcription factor NF-kB and one of its target genes called GLUT3.

This work reveals an additional function of p53 in restricting cell proliferation through suppression of NF-kB, which is important for maintaining normal levels of glucose metabolism and cell growth.

Author contact:
Nobuyuki Tanaka (Nippon Medical School, Kawasaki-shi, Japan)
Tel: +81 44 733 1860; E-mail: nobuta@nms.ac.jp

Mitochondrial downfall in Parkinson’s disease



The mutation of two genes associated with the development of Parkinson’s disease cooperate to regulate mitochondrial function when cells are stressed. This link will help researchers understand the mechanisms underlying the neuronal degeneration seen in pathologies such as Parkinson‘s disease.

Julian Downward and colleagues investigated the mitochondrial protease Omi – the loss of which leads to a neurodegenerative disorder resembling Parkinson’s. They found that Omi is regulated by PINK1, which has been identified as an early-onset Parkinson’s disease susceptibility factor. The researchers show that, in response to various cellular stresses, PINK1 is essential for mitochondrial protection by Omi and keeps cells healthy. Strikingly, they also find that this cooperation is impaired in brain samples from Parkinson's disease patients carrying mutations in PINK1.

Finding this new interaction suggests that in the normal brain, PINK1 and Omi prevent the death of neuronal cells by protecting their mitochondria. The development of Parkinson’s disease would thus be linked to a higher susceptibility to neuronal death following stress.


Author contact:

Julian Downward (Cancer Research UK, London, UK)

Tel: +44 207 269 3533; E-mail: julian.downward@cancer.org.uk