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RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2 (2014)
Journal Article
Pefani, D., Latusek, R., Pires, I., Grawenda, A. M., Yee, K. S., Hamilton, G., …O'Neill, E. (2014). RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2. Nature Cell Biology, 16(10), 962-971. https://doi.org/10.1038/ncb3035

Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. ​BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting ​RAD51 nucleofilament formation at stal... Read More about RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2.

HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion (2014)
Journal Article
Poujade, F., Harvey, A. J., Blokland, N. J. G., Broos, A. W. T., Eccles, S. A., Hammond, E. M., …Span, P. N. (2014). HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion. Cancer Biology and Therapy, 15(10), 1350-1357. https://doi.org/10.4161/cbt.29822

© 2014 Landes Bioscience. PTK6/Brk is a non-receptor tyrosine kinase overexpressed in cancer. Here we demonstrate that cytosolic PTK6 is rapidly and robustly induced in response to hypoxic conditions in a HIF-1-independent manner. Furthermore, a prop... Read More about HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion.

Replication stress and chromatin context link ATM activation to a role in DNA replication (2013)
Journal Article
Olcina, M. M., Foskolou, I. P., Anbalagan, S., Senra, J. M., Pires, I. M., Jiang, Y., …Hammond, E. M. (2013). Replication stress and chromatin context link ATM activation to a role in DNA replication. Molecular cell, 52(5), 758-766. https://doi.org/10.1016/j.molcel.2013.10.019

ATM-mediated signaling in response to DNA damage is a barrier to tumorigenesis. Here we asked whether replication stress could also contribute to ATM signaling. We demonstrate that, in the absence of DNA damage, ATM responds to replication stress in... Read More about Replication stress and chromatin context link ATM activation to a role in DNA replication.

CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and aurora A (2013)
Journal Article
Cazares-Körner, C., Pires, I. M., Swallow, I. D., Grayer, S. C., O'Connor, L. J., Olcina, M. M., …Hammond, E. M. (2013). CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and aurora A. ACS Chemical Biology, 8(7), 1451-1459. https://doi.org/10.1021/cb4001537

The increased resistance of hypoxic cells to all forms of cancer therapy presents a major barrier to the successful treatment of most solid tumors. Inhibition of the essential kinase Checkpoint kinase 1 (Chk1) has been described as a promising cancer... Read More about CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and aurora A.

Use of the xCELLigence system for real-time analysis of changes in cellular motility and adhesion in physiological conditions (2013)
Journal Article
Scrace, S., O'Neill, E., Hammond, E. M., & Pires, I. M. (2013). Use of the xCELLigence system for real-time analysis of changes in cellular motility and adhesion in physiological conditions. Methods in molecular biology, 1046, 295-306. https://doi.org/10.1007/978-1-62703-538-5_17

Investigation of the mechanisms behind the regulation of cellular motility and adhesion is key to understanding metastasis and the biology of tumor spreading. There are many technologies available for these studies, but the majority of them are eithe... Read More about Use of the xCELLigence system for real-time analysis of changes in cellular motility and adhesion in physiological conditions.

Targeting radiation-resistant hypoxic tumour cells through ATR inhibition (2012)
Journal Article
Monteiro dos Santos Pires, I., Olcina, M. M., Anbalagan, S., Pollard, J. R., Reaper, P. M., Charlton, P. A., …Hammond, E. M. (2012). Targeting radiation-resistant hypoxic tumour cells through ATR inhibition. The British Journal of Cancer, 107(2), 291-299. https://doi.org/10.1038/bjc.2012.265

Background:Most solid tumours contain regions of sub-optimal oxygen concentration (hypoxia). Hypoxic cancer cells are more resistant to radiotherapy and represent the most aggressive fraction of a tumour. It is therefore essential that strategies con... Read More about Targeting radiation-resistant hypoxic tumour cells through ATR inhibition.

Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy (2012)
Journal Article
Anbalagan, S., Monteiro dos Santos Pires, I., Blick, C., Hill, M. A., Ferguson, D. J. P., Chan, D. A., & Hammond, E. M. (2012). Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 103(3), 388-393. https://doi.org/10.1016/j.radonc.2012.04.001

Background and purpose: For patients diagnosed with advanced renal cell carcinoma (RCC), there are few therapeutic options. Radiation therapy is predominantly used to treat metastasis and has not proven effective in the adjuvant setting for renal can... Read More about Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy.

Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1α (2011)
Journal Article
Coutts, A. S., Pires, I. M., Weston, L., Buffa, F. M., Milani, M., Li, J., …La Thangue, N. B. (2011). Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1α. Oncogene, 30(48), 4835-4842. https://doi.org/10.1038/onc.2011.188

Junction-mediating and regulatory protein (JMY) is a novel p53 cofactor that regulates p53 activity during stress. JMY interacts with p300/CBP, which are ubiquitous transcriptional co-activators that interact with a variety of sequence-specific trans... Read More about Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1α.

Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment (2010)
Journal Article
Chan, N., Pires, I. M., Bencokova, Z., Coackley, C., Luoto, K. R., Bhogal, N., …Bristow, R. G. (2010). Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Cancer Research, 70(20), 8045-8054. https://doi.org/10.1158/0008-5472.CAN-10-2352

Acute and chronic hypoxia exists within the three-dimensional microenvironment of solid tumors and drives therapy resistance, genetic instability, and metastasis. Replicating cells exposed to either severe acute hypoxia (16 hours with 0.02% O 2 ) fol... Read More about Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment.

Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1 (2010)
Journal Article
Pires, I. M., Bencokova, Z., Hammond, E. M., & McGurk, C. (2010). Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1. Cell cycle, 9(13), 2502-2507. https://doi.org/10.4161/cc.9.13.12059

Severe hypoxia has been demonstrated to induce a replication arrest which is associated with decreased levels of nucleotides. Chk1 is rapidly phosphorylated in response to severe hypoxia and in turn deactivates TLK1 through phosphorylation. Loss of C... Read More about Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1.

Regulation of autophagy by ATF4 in response to severe hypoxia (2010)
Journal Article
Rzymski, T., Milani, M., Pike, L., Buffa, F., Mellor, H. R., Winchester, L., …Harris, A. L. (2010). Regulation of autophagy by ATF4 in response to severe hypoxia. Oncogene, 29(31), 4424-4435. https://doi.org/10.1038/onc.2010.191

Activating transcription factor 4 (ATF4) is a transcription factor induced under severe hypoxia and a component of the PERK pathway involved in the unfolded protein response (UPR), a process that protects cells from the negative consequences of endop... Read More about Regulation of autophagy by ATF4 in response to severe hypoxia.

Oxaliplatin responses in colorectal cancer cells are modulated by CHK2 kinase inhibitors (2010)
Journal Article
Pires, I. M., Ward, T. H., & Dive, C. (2010). Oxaliplatin responses in colorectal cancer cells are modulated by CHK2 kinase inhibitors. British Journal of Pharmacology, 159(6), 1326-1338. https://doi.org/10.1111/j.1476-5381.2009.00607.x

Background and purpose: Checkpoint kinase 2 (CHK2) is activated by DNA damage and can contribute to p53 stabilization, modulating growth arrest and/or apoptosis. We investigated the contribution of CHK2 to oxaliplatin-mediated toxicity in a colorecta... Read More about Oxaliplatin responses in colorectal cancer cells are modulated by CHK2 kinase inhibitors.

Effects of acute versus chronic hypoxia on DNA damage responses and genomic instability (2010)
Journal Article
Pires, I. M., Bencokova, Z., Milani, M., Folkes, L. K., Li, J., Stratford, M. R., …Hammond, E. M. (2010). Effects of acute versus chronic hypoxia on DNA damage responses and genomic instability. Cancer Research, 70(3), 925-935. https://doi.org/10.1158/0008-5472.CAN-09-2715

Questions exist concerning the effects of acute versus chronic hypoxic conditions on DNA replication and genomic stability that may influence tumorigenesis. Severe hypoxia causes replication arrest independent of S-phase checkpoint, DNA damage respon... Read More about Effects of acute versus chronic hypoxia on DNA damage responses and genomic instability.

ATM activation and signaling under hypoxic conditions (2008)
Journal Article
Bencokova, Z., Kaufmann, M. R., Monteiro dos Santos Pires, I., Lecane, P. S., Giaccia, A. J., & Hammond, E. M. (2009). ATM activation and signaling under hypoxic conditions. Molecular and cellular biology, 29(2), 526-537. https://doi.org/10.1128/MCB.01301-08

The ATM kinase has previously been shown to respond to the DNA damage induced by reoxygenation following hypoxia by initiating a Chk 2-dependent cell cycle arrest in the G2 phase. Here we show that ATM is both phosphorylated and active during exposur... Read More about ATM activation and signaling under hypoxic conditions.

Fission yeast Dss1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis (2006)
Journal Article
Jossé, L., Harley, M. E., Monteiro dos Santos Pires, I., & Hughes, D. A. (2006). Fission yeast Dss1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis. Biochemical Journal, 393(1), 303-309. https://doi.org/10.1042/BJ20051238

Human DSS1 associates with BRCA2, a tumour suppressor protein required for efficient recombinational DNA repair, but the biochemical function of DSS1 is not known. Orthologues of DSS1 are found in organisms such as budding yeast and fission yeast tha... Read More about Fission yeast Dss1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis.