Increased mitochondrial proline metabolism sustains proliferation and survival of colorectal cancer cells.

Autor: Saif Sattar Alaqbi, Lynsey Burke, Inna Guterman, Caleb Green, Kevin West, Raquel Palacios-Gallego, Hong Cai, Constantinos Alexandrou, Ni Ni Moe Myint, Emma Parrott, Lynne M Howells, Jennifer A Higgins, Donald J L Jones, Rajinder Singh, Robert G Britton, Cristina Tufarelli, Anne Thomas, Alessandro Rufini

Publikováno v: PLoS ONE, Vol 17, Iss 2, p e0262364 (2022)

Research into the metabolism of the non-essential amino acid (NEAA) proline in cancer has gained traction in recent years. The last step in the proline biosynthesis pathway is catalyzed by pyrroline-5-carboxylate reductase (PYCR) enzymes. There are t

Externí odkaz: https://doaj.org/article/a8c59ad1f4bd4b7cb6c22cc96e695c6e

Data from MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression

Autor: Owen J. Sansom, Martin Bushell, Anne E. Willis, Joanne Edwards, John Le Quesne, William J. Faller, Heather J. McKinnon, Martin E. Swarbrick, Neil P. Jones, Christopher G. Proud, Nahum Sonenberg, Kevin M. Haigis, Nicola Valeri, Georgios Vlachogiannis, Andrew D. Campbell, Joseph A. Waldron, Rene Jackstadt, Joshua D. Leach, Emma Stanway, Kerri McArthur, Anne Cheasty, Craig MacKay, Laura McDonald, Rachael C.L. Smith, Dustin J. Flanagan, Rachel A. Ridgway, Kathryn Gilroy, Arafath K. Najumudeen, Ewan M. Smith, Sebastian May-Wilson, David M. Gay, Georgios Kanellos, Ana Teodosio, Leah Officer, Kathryn Pennel, Nikola Vlahov, George L. Skalka, Constantinos Alexandrou, John R.P. Knight

KRAS-mutant colorectal cancers are resistant to therapeutics, presenting a significant problem for ∼40% of cases. Rapalogs, which inhibit mTORC1 and thus protein synthesis, are significantly less potent in KRAS-mutant colorectal cancer. Using Kras-

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f56670615fce027f717d8d9f47081b8
https://doi.org/10.1158/2159-8290.c.6549409

MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression

Autor: Anne E. Willis, Laura McDonald, George Skalka, Andrew D. Campbell, Heather McKinnon, Kevin M. Haigis, John R. P. Knight, Sebastian May-Wilson, Kathryn Gilroy, William J. Faller, Emma Stanway, Leah Officer, Rachael C. L. Smith, Joshua D.G. Leach, Joseph A. Waldron, Rachel A. Ridgway, Nicola Valeri, Ewan M. Smith, Arafath Kaja Najumudeen, Nahum Sonenberg, Joanne Edwards, Rene Jackstadt, Ana Teodósio, John Le Quesne, Dustin J. Flanagan, Anne Cheasty, Georgios Kanellos, Kerri McArthur, Christopher G. Proud, Constantinos Alexandrou, Georgios Vlachogiannis, Neil P. Jones, Nikola Vlahov, Owen J. Sansom, Kathryn Af Pennel, Craig MacKay, Martin E. Swarbrick, Martin Bushell

Publikováno v: Knight, J R P, Alexandrou, C, Skalka, G L, Vlahov, N, Pennel, K, Officer, L, Teodosio, A, Kanellos, G, Gay, D M, May-Wilson, S, Smith, E M, Najumudeen, A K, Gilroy, K, Ridgway, R A, Flanagan, D J, Smith, R C L, McDonald, L, MacKay, C, Cheasty, A, McArthur, K, Stanway, E, Leach, J D, Jackstadt, R, Waldron, J A, Campbell, A D, Vlachogiannis, G, Valeri, N, Haigis, K M, Sonenberg, N, Proud, C G, Jones, N P, Swarbrick, M E, McKinnon, H J, Faller, W J, Quesne, J L, Edwards, J, Willis, A E, Bushell, M & Sansom, O J 2021, ' MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression ', Cancer discovery, vol. 11, no. 5, pp. 1228-1247 . https://doi.org/10.1158/2159-8290.CD-20-0652

KRAS-mutant colorectal cancers are resistant to therapeutics, presenting a significant problem for ∼40% of cases. Rapalogs, which inhibit mTORC1 and thus protein synthesis, are significantly less potent in KRAS-mutant colorectal cancer. Using Kras-

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4b093ca20383c7ab94bac414895dbf3
https://doi.org/10.1158/2159-8290.CD-20-0652

Sensitivity of Colorectal Cancer to Arginine Deprivation Therapy is Shaped by Differential Expression of Urea Cycle Enzymes

Autor: Constantinos Alexandrou, Jin-Li Luo, Anne Thomas, Maria Viskaduraki, Karen Brown, Jennifer A. Higgins, Alessandro Rufini, Saif Sattar Al-Aqbi, Matthew Blades, Lynne M. Howells, William K. Boyle, Paul N. Cheng, Graeme I. Murray, David Moore, Ankur Karmokar, Catherine Andreadi

Publikováno v: Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
Scientific Reports

Tumors deficient in the urea cycle enzymes argininosuccinate synthase-1 (ASS1) and ornithine transcarbamylase (OTC) are unable to synthesize arginine and can be targeted using arginine-deprivation therapy. Here, we show that colorectal cancers (CRCs)

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b34191506b0929fe0c27a768215b1f15
http://link.springer.com/article/10.1038/s41598-018-30591-7