Molecular alterations that drive breast cancer metastasis to bone.

Epithelial cancers including breast and prostate commonly progress to form incurable bone metastases. For this to occur, cancer cells must adapt their phenotype and behaviour to enable detachment from the primary tumour, invasion into the vasculature, and homing to and subsequent colonisation of bone. It is widely accepted that the metastatic process is driven by the transformation of cancer cells from a sessile epithelial to a motile mesenchymal phenotype through epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into the circulation provides the conduit for cells to metastasise to distant organs. However, accumulating evidence suggests that EMT is not sufficient for metastasis to occur and that specific tissue-homing factors are required for tumour cells to lodge and grow in bone. Once tumour cells are disseminated in the bone environment, they can revert into an epithelial phenotype through the reverse process of mesenchymal-epithelial transition (MET) and form secondary tumours. In this review, we describe the molecular alterations undertaken by breast cancer cells at each stage of the metastatic cascade and discuss how these changes facilitate bone metastasis

The Chlamydomonas CO2-concentrating mechanism and its potential for engineering photosynthesis in plants

To meet the food demands of a rising global population, innovative strategies are required to increase crop yields. Improvements in plant photosynthesis by genetic engineering show considerable potential towards this goal. One prospective approach is to introduce a CO2-concentrating mechanism into crop plants to increase carbon fixation by supplying the central carbon-fixing enzyme, Rubisco, with a higher concentration of its substrate, CO2. A promising donor organism for the molecular machinery of this mechanism is the eukaryotic alga Chlamydomonas reinhardtii. This review summarizes the recent advances in our understanding of carbon concentration in Chlamydomonas, outlines the most pressing gaps in our knowledge and discusses strategies to transfer a CO2-concentrating mechanism into higher plants to increase photosynthetic performance

Pyrenoid loss impairs carbon-concentrating mechanism induction and alters primary metabolism in Chlamydomonas reinhardtii

Carbon-concentrating mechanisms (CCMs) enable efficient photosynthesis and growth in CO2-limiting environments, and in eukaryotic microalgae localisation of Rubisco to a microcompartment called the pyrenoid is key. In the model green alga Chlamydomonas reinhardtii, Rubisco preferentially relocalises to the pyrenoid during CCM induction and pyrenoid-less mutants lack a functioning CCM and grow very poorly at low CO2. The aim of this study was to investigate the CO2 response of pyrenoid-positive (pyr+) and pyrenoid-negative (pyr–) mutant strains to determine the effect of pyrenoid absence on CCM induction and gene expression. Shotgun proteomic analysis of low-CO2-adapted strains showed reduced accumulation of some CCM-related proteins, suggesting that pyr– has limited capacity to respond to low-CO2 conditions. Comparisons between gene transcription and protein expression revealed potential regulatory interactions, since Rubisco protein linker (EPYC1) protein did not accumulate in pyr– despite increased transcription, while elements of the LCIB/LCIC complex were also differentially expressed. Furthermore, pyr− showed altered abundance of a number of proteins involved in primary metabolism, perhaps due to the failure to adapt to low CO2. This work highlights two-way regulation between CCM induction and pyrenoid formation, and provides novel candidates for future studies of pyrenoid assembly and CCM function