Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
AI Summary:
Pancreatic ductal adenocarcinoma has a poor prognosis due to high rates of metastasis and limited treatment options. CYRI-B, a protein highly expressed in pancreatic tumours, plays a role in growth and signalling in pancreatic cancer.AI Topics:
Pancreatic ductal adenocarcinoma carries a dismal prognosis, with high rates of metastasis and few treatment options. Hyperactivation of KRAS in almost all tumours drives RAC1 activation, conferring enhanced migratory and proliferative capacity as well as macropinocytosis. Macropinocytosis is well understood as a nutrient scavenging mechanism, but little is known about its functions in trafficking of signalling receptors. We find that CYRI-B is highly expressed in pancreatic tumours in a mouse model of KRAS and p53-driven pancreatic cancer. Deletion of Cyrib (the gene encoding CYRI-B protein) accelerates tumourigenesis, leading to enhanced ERK and JNK-induced proliferation in precancerous lesions, indicating a potential role as a buffer of RAC1 hyperactivation in early stages. However, as disease progresses, loss of CYRI-B inhibits metastasis. CYRI-B depleted tumour cells show reduced chemotactic responses to lysophosphatidic acid, a major driver of tumour spread, due to impaired macropinocytic uptake of the lysophosphatidic acid receptor 1. Overall, we implicate CYRI-B as a mediator of growth and signalling in pancreatic cancer, providing new insights into pathways controlling metastasis.
Nikolaou, Savvas
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
See full publications listJuin, Amelie
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
See full publications listWhitelaw, Jamie
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
Kapitany, Valentin and Fatima, Areeba and Zickus, Vytautas and Whitelaw, Jamie and McGhee, Ewan and Insall, Robert and Machesky, Laura and Faccio, Daniele (2024) Single-sample image-fusion upsampling of fluorescence lifetime images. Science Advances, 10 (21): eadn0139. ISSN 2375-2548
See full publications listPaul, Nikki R.
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
Mandrou, Elena and Thomason, Peter A. and Paschke, Peggy I. and Paul, Nikki R. and Tweedy, Luke and Insall, Robert (2024) A reliable system for quantitative g-protein activation imaging in cancer cells. Cells, 13 (13): 1114. ISSN 2073-4409
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listFort, Loic
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
See full publications listNixon, Colin
Author
Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.
Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X
Churchhouse, Antonia M.D. and Billard, Caroline V. and Suzuki, Toshiyasu and Pohl, Sebastian O.G. and Donnelly, Kevin and Nixon, Colin and Arends, Mark J. and Din, Shahida and Kirkwood, Kathryn and Marques Junior, Jair and Von Kriegsheim, Alexander and Coffelt, Seth B. and Myant, Kevin B. (2024) Loss of DOCK2 potentiates Inflammatory Bowel Disease-associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression. Oncogene, 43 (42). pp. 3094-3107. ISSN 0950-9232
See full publications listSpence, Heather J.
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
Juin, Amelie and Spence, Heather J. and Machesky, Laura M. (2024) Dichotomous role of the serine/threonine kinase MAP4K4 in pancreatic ductal adenocarcinoma onset and metastasis through control of AKT and ERK pathways. Journal of Pathology, 262 (4). pp. 454-466. ISSN 0022-3417
See full publications listBryson, Sheila
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
See full publications listMachesky, Laura
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
Kapitany, Valentin and Fatima, Areeba and Zickus, Vytautas and Whitelaw, Jamie and McGhee, Ewan and Insall, Robert and Machesky, Laura and Faccio, Daniele (2024) Single-sample image-fusion upsampling of fluorescence lifetime images. Science Advances, 10 (21): eadn0139. ISSN 2375-2548
Juin, Amelie and Spence, Heather J. and Machesky, Laura M. (2024) Dichotomous role of the serine/threonine kinase MAP4K4 in pancreatic ductal adenocarcinoma onset and metastasis through control of AKT and ERK pathways. Journal of Pathology, 262 (4). pp. 454-466. ISSN 0022-3417
See full publications listAvailable under License Creative Commons Attribution.
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