Professor Gareth Inman

Professor (Beatson Institute for Cancer Research)
Director of Research (School of Cancer Sciences)

email: Gareth.Inman@glasgow.ac.uk
pronouns: He/him/his

Research interests

Growth factor signalling and squamous cancers

The transforming growth factor beta (TGFβ) superfamily comprises approximately forty related dimeric polypeptide cytokines including the bone morphogenetic proteins (BMPs), the growth and differentiation factors (GDFs), activin, nodal and the TGFβs (TGFβ1, TGFβ2, TGFβ3). As well as having vital normal physiological functions during development and in adult life these factors play pivotal roles in cancer biology acting as potent tumour suppressors or tumour promoters in a context dependent manner. Work in our laboratory seeks to understand how, when and where TGF superfamily signalling regulates tumour progression. Dysregulation of TGF signalling is particularly prevalent in squamous cell cancers and this has led us to begin to decipher the molecular landscape of cutaneous squamous cell carcinoma and its similarities with other squamous tumour subtypes. Our work focuses on understanding the driver genes, pathways and processes that drive squamous cancer disease progression with particular focus on cSCC, Head and Neck SCC and the “squamous” subtype of pancreatic cancer using in-vitro, ex-vivo and in-vivo pre-clinical models.

Research groups

Cancer Hallmarks to Novel Therapies
Cancer Evolution in Time & Space
Immunology & Cancer
Comprehensive Cancer Models
Re-imagining Radiotherapy

Publications

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Number of items: 71.

2024

Singh, S. P. et al. (2024) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, (doi: 10.1038/s44319-024-00323-2) (Early Online Publication)

Kiourtis, C. et al. (2024) Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ. Nature Cell Biology, (doi: 10.1038/s41556-024-01543-3) (PMID:39537753) (Early Online Publication)

Smith, C. D.L., McMahon, A. D. , Purkayastha, M., Creaney, G. , Clements, K., Inman, G. J. , Bhatti, L. A., Douglas, C. M., Paterson, C. and Conway, D. I. (2024) Head and neck cancer incidence is rising but the sociodemographic profile is unchanging: a population epidemiological study (2001-2020). BJC Reports, 2, 71. (doi: 10.1038/s44276-024-00089-z) (PMID:39301277)

Strathearn, L. S., Spender, L. C., Schoenherr, C., Mason, S., Edwards, R., Blyth, K. and Inman, G. (2024) C1orf106 (INAVA) is a SMAD3-dependent TGF-β target gene that promotes clonogenicity and correlates with poor prognosis in breast cancer. Cells, 13(18), 1530. (doi: 10.3390/cells13181530)

Smith, C. D.L. et al. (2024) Development and external validation of a head and neck cancer risk prediction model. Head and Neck, 46(9), pp. 2261-2273. (doi: 10.1002/hed.27834) (PMID:38850089)

Derby, S. et al. (2024) Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalisation via macropinocytosis. Neuro-Oncology, (doi: 10.1093/neuonc/noad210) (PMID:37936324) (Early Online Publication)

2023

Wang, J. et al. (2023) Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multigene prognostic signature associated with metastasis. Journal of the American Academy of Dermatology, 89(6), pp. 1159-1166. (doi: 10.1016/j.jaad.2023.08.012) (PMID:37586461)

Bailey, P. et al. (2023) Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression. Nature Communications, 14, 5211. (doi: 10.1038/s41467-023-40822-9) (PMID:37626054) (PMCID:PMC10457401)

2022

Flanagan, D. J. et al. (2022) Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features. Nature Communications, 13, 7551. (doi: 10.1038/s41467-022-35134-3) (PMID:36477656) (PMCID:PMC9729215)

Smith, C. D.L., McMahon, A. D. , Ross, A. , Inman, G. J. and Conway, D. I. (2022) Risk prediction models for head and neck cancer: a rapid review. Laryngoscope Investigative Otolaryngology, 7(6), pp. 1893-1908. (doi: 10.1002/lio2.982) (PMID:36544947) (PMCID:PMC9764804)

2021

Hollis, R. L. et al. (2021) Clinicopathological determinants of recurrence risk and survival in mucinous ovarian carcinoma. Cancers, 13(22), e5839. (doi: 10.3390/cancers13225839) (PMID:34830992) (PMCID:PMC8616033)

Birch, J. et al. (2021) Inhibition of ATR prevents macropinocytosis driven retraction of neurites and opposes invasion in GBM. Research Square, (doi: 10.21203/rs.3.rs-967109/v1) (PMID:37936324)

Leach, J. D.G. et al. (2021) Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis. Nature Communications, 12, 3464. (doi: 10.1038/s41467-021-23717-5) (PMID:34103493) (PMCID:PMC8187652)

2020

Wei, Q., Young, J., Holle, A., Li, J., Bieback, K., Inman, G. , Spatz, J. P. and Cavalcanti-Adam, E. A. (2020) Soft hydrogels for balancing cell proliferation and differentiation. ACS Biomaterials Science and Engineering, 6(8), pp. 4687-4701. (doi: 10.1021/acsbiomaterials.0c00854) (PMID:33455192)

Wei, Q. et al. (2020) BMP‐2 signaling and mechanotransduction synergize to drive osteogenic differentiation via YAP/TAZ. Advanced Science, 7(15), 1902931. (doi: 10.1002/advs.201902931) (PMID:32775147) (PMCID:PMC7404154)

2019

Badshah, I.I., Brown, S., Weibel, L., Rose, A., Way, B., Sebire, N., Inman, G. , Harper, J. and O'Shaughnessy, R.F.L. (2019) Differential expression of secreted factors SOSTDC1 and ADAMTS8 cause profibrotic changes in linear morphoea fibroblasts. British Journal of Dermatology, 180(5), pp. 1135-1149. (doi: 10.1111/bjd.17352) (PMID:30367460)

Spender, L. C. et al. (2019) Preclinical evaluation of AZ12601011 and AZ12799734, inhibitors of transforming growth factor β superfamily type 1 receptors. Molecular Pharmacology, 95(2), pp. 222-234. (doi: 10.1124/mol.118.112946) (PMID:30459156)

Hassan, S. et al. (2019) A unique panel of patient-derived cutaneous squamous cell carcinoma cell lines provides a preclinical pathway for therapeutic testing. International Journal of Molecular Sciences, 20(14), 3428. (doi: 10.3390/ijms20143428) (PMID:31336867) (PMCID:PMC6678499)

2018

Inman, G. J. et al. (2018) The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature. Nature Communications, 9, 3667. (doi: 10.1038/s41467-018-06027-1) (PMID:30202019) (PMCID:PMC6131170)

Purdie, K. J. et al. (2018) The role of human papillomaviruses and polyomaviruses in BRAF-inhibitor induced cutaneous squamous cell carcinoma and benign squamoproliferative lesions. Frontiers in Microbiology, 9, 1806. (doi: 10.3389/fmicb.2018.01806) (PMID:30154763) (PMCID:PMC6102365)

Rose, A. M. et al. (2018) Reduced SMAD2/3 activation independently predicts increased depth of human cutaneous squamous cell carcinoma. Oncotarget, 9(18), pp. 14552-14566. (doi: 10.18632/oncotarget.24545) (PMID:29581863) (PMCID:PMC5865689)

Hurst, L. A. et al. (2018) TNFα drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling. Nature Communications, 8, 14079. (doi: 10.1038/ncomms14079) (PMID:28084316) (PMCID:PMC5241886)

2017

Cammareri, P. et al. (2017) TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis. Cell Death and Differentiation, 24(10), pp. 1681-1693. (doi: 10.1038/cdd.2017.92) (PMID:28622298)

Phillips, T. J. et al. (2017) Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development. Scientific Reports, 7, 9079. (doi: 10.1038/s41598-017-06300-1) (PMID:28831049) (PMCID:PMC5567270)

Spender, L. C. and Inman, G. J. (2017) Targeting BRAF-mutant tumours with TGFBR1 inhibitors. Aging, 9(1), pp. 5-6. (doi: 10.18632/aging.101169) (PMID:28148904) (PMCID:PMC5310652)

Rose, A. M., Sansom, O. J. and Inman, G. J. (2017) Loss of TGF-β signaling drives cSCC from skin stem cells – More evidence. Cell Cycle, 16(5), pp. 386-387. (doi: 10.1080/15384101.2016.1259892) (PMID:27860538) (PMCID:PMC5351926)

2016

Spender, L. C. et al. (2016) Mutational activation of BRAF confers sensitivity to transforming growth factor beta inhibitors in human cancer cells. Oncotarget, 7(50), pp. 81995-82012. (doi: 10.18632/oncotarget.13226) (PMID:27835901) (PMCID:PMC5347669)

Cammareri, P. et al. (2016) Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma. Nature Communications, 7, 12493. (doi: 10.1038/ncomms12493) (PMID:27558455) (PMCID:PMC5007296)

Languino, L. R., Singh, A., Prisco, M., Inman, G. J. , Luginbuhl, A., Curry, J. M. and South, A. P. (2016) Exosome-mediated transfer from the tumor microenvironment increases TGFβ signaling in squamous cell carcinoma. American Journal of Translational Research, 8(5), pp. 2432-2437. (PMID:27347352) (PMCID:PMC4891457)

Harwood, C. A., Proby, C. M., Inman, G. J. and Leigh, I. M. (2016) The promise of genomics and the development of targeted therapies for cutaneous squamous cell carcinoma. Acta Dermato Venereologica, 96(1), pp. 3-16. (doi: 10.2340/00015555-2181) (PMID:26084328)

Spender, L.C. and Inman, G.J. (2016) Fatal attractions? Correlations of CXCL12-CXCR4-CXCR7 expression with disease progression in melanoma and Kaposi sarcoma. British Journal of Dermatology, 175(6), pp. 1140-1141. (doi: 10.1111/bjd.15136) (PMID:27996149)

2014

MacKay, C., Carroll, E., Ibrahim, A. F.M., Garg, A., Inman, G. J. , Hay, R. T. and Alpi, A. F. (2014) E3 ubiquitin ligase HOIP attenuates apoptotic cell death induced by cisplatin. Cancer Research, 74(8), pp. 2246-2257. (doi: 10.1158/0008-5472.CAN-13-2131) (PMID:24686174) (PMCID:PMC3990471)

Spender, L. C. and Inman, G. J. (2014) Developments in Burkitt's lymphoma: novel cooperations in oncogenic MYC signaling. Cancer Management and Research, 6, pp. 27-38. (doi: 10.2147/CMAR.S37745) (PMID:24426788) (PMCID:PMC3890408)

2013

Herrera, B., García-Álvaro, M., Cruz, S., Walsh, P., Fernández, M., Roncero, C., Fabregat, I., Sánchez, A. and Inman, G. J. (2013) BMP9 is a proliferative and survival factor for human hepatocellular carcinoma cells. PLoS ONE, 8(7), e69535. (doi: 10.1371/journal.pone.0069535) (PMID:23936038) (PMCID:PMC3720667)

Nigro, C. L. et al. (2013) Methylated Tissue Factor Pathway Inhibitor 2 (TFPI2) DNA in serum is a biomarker of metastatic melanoma. Journal of Investigative Dermatology, 133(5), pp. 1278-1285. (doi: 10.1038/jid.2012.493) (PMID:23407390)

Brkljacic, J., Pauk, M., Erjavec, I., Cipcic, A., Grgurevic, L., Zadro, R., Inman, G. J. and Vukicevic, S. (2013) Exogenous heparin binds and inhibits bone morphogenetic protein 6 biological activity. International Orthopaedics, 37(3), pp. 529-541. (doi: 10.1007/s00264-012-1714-3) (PMID:23307015) (PMCID:PMC3580086)

Spender, L.C., Carter, M.J., O'Brien, D.I., Clark, L.J., Yu, J., Michalak, E.M., Happo, L., Cragg, M.S. and Inman, G.J. (2013) Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas. Journal of Biological Chemistry, 288(7), pp. 5198-5209. (doi: 10.1074/jbc.M112.410274) (PMID:23243310) (PMCID:PMC3576124)

Acosta, J.C. et al. (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nature Cell Biology, 15, pp. 978-990. (doi: 10.1038/ncb2784)

2012

Wang, H. et al. (2012) NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. British Journal of Cancer, 106(8), pp. 1446-1452. (doi: 10.1038/bjc.2012.95) (PMID:22454080) (PMCID:PMC3326678)

Spender, L. C. and Inman, G. J. (2012) Phosphoinositide 3-kinase/AKT/mTORC1/2 signaling determines sensitivity of Burkitt's lymphoma cells to BH3 mimetics. Molecular Cancer Research, 10(3), pp. 347-359. (doi: 10.1158/1541-7786.MCR-11-0394) (PMID:22241218) (PMCID:PMC3378513)

Elston, R. and Inman, G. J. (2012) Crosstalk between p53 and TGF-β signalling. Journal of Signal Transduction, 2012, 294097. (doi: 10.1155/2012/294097) (PMID:22545213) (PMCID:PMC3321553)

2011

Inman, G. J. (2011) Switching TGFβ from a tumor suppressor to a tumor promoter. Current Opinion in Genetics and Development, 21(1), pp. 93-99. (doi: 10.1016/j.gde.2010.12.004) (PMID:21251810)

Morin, P., Wickman, G., Munro, J., Inman, G.J. and Olson, M.F. (2011) Differing contributions of LIMK and ROCK to TGFβ-induced transcription, motility and invasion. European Journal of Cell Biology, 90(1), pp. 13-25. (doi: 10.1016/j.ejcb.2010.09.009) (PMID:21074289)

Spender, L. C. and Inman, G. J. (2011) Inhibition of germinal centre apoptotic programmes by Epstein-Barr Virus. Advances in Hematology, 2011, 829525. (doi: 10.1155/2011/829525) (PMID:22110506) (PMCID:PMC3202104)

2010

Pellicano, F., Thomson, R.E., Inman, G.J. and Iwata, T. (2010) Regulation of cell proliferation and apoptosis in neuroblastoma cells by ccp1, a FGF2 downstream gene. BMC Cancer, 10(1), 657. (doi: 10.1186/1471-2407-10-657) (PMID:21118521) (PMCID:PMC3001724)

Calaminus, S. D., Inman, G. , Ghaevert, C., Sansom, O. , Watson, S. P., Holyoake, T. L. and Machesky, L. (2010) Alterations In Wnt Signalling In the Megakaryocytic Lineage Leads to Bone Marrow Failure and Myelofibrosis. Blood, 116(21), 628. (doi: 10.1182/blood.V116.21.628.628)

Hannigan, A. et al. (2010) Epigenetic downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to a tumor promoter. Journal of Clinical Investigation, 120(8), pp. 2842-2857. (doi: 10.1172/JCI36125) (PMID:20592473) (PMCID:PMC2912175)

2009

Herrera, B., van Dinther, M., ten Dijke, P. and Inman, G. J. (2009) Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation. Cancer Research, 69(24), pp. 9254-9262. (doi: 10.1158/0008-5472.CAN-09-2912) (PMID:19996292) (PMCID:PMC2892305)

Herrera, B. and Inman, G. J. (2009) A rapid and sensitive bioassay for the simultaneous measurement of multiple bone morphogenetic proteins. Identification and quantification of BMP4, BMP6 and BMP9 in bovine and human serum. BMC Cell Biology, 10, 20. (doi: 10.1186/1471-2121-10-20) (PMID:19298647) (PMCID:PMC2663541)

Spender, L. C. and Inman, G. J. (2009) TGF-β Induces growth arrest in Burkitt lymphoma cells via transcriptional repression of E2F-1. Journal of Biological Chemistry, 284(3), pp. 1435-1442. (doi: 10.1074/jbc.m808080200) (PMID:19022773)

Fleming, Y.M., Ferguson, G.J., Spender, L., Larsson, J., Karlsson, S., Ozanne, B.W., Grosse, R. and Inman, G.J. (2009) TGF-β-mediated activation of RhoA signalling is required for efficient V12HaRas and V600EBRAF transformation. Oncogene, 28(7), pp. 983-993. (doi: 10.1038/onc.2008.449) (PMID:19079344)

Spender, L.C., O'Brien, D.I., Simpson, D., Dutt, D., Gregory, C.D., Allday, M.J., Clark, L.J. and Inman, G.J. (2009) TGF-β induces apoptosis in human B cells by transcriptional regulation of BIK and BCL-XL. Cell Death and Differentiation, 16(4), pp. 593-602. (doi: 10.1038/cdd.2008.183) (PMID:19136942) (PMCID:PMC2857326)

Spender, L. C. and Inman, G. J. (2009) Targeting the BCL-2 family in malignancies of germinal centre origin. Expert Opinion on Therapeutic Targets, 13(12), pp. 1459-1472. (doi: 10.1517/14728220903379565) (PMID:19922301)

2008

Frame, M. C. and Inman, G. J. (2008) NCAM Is at the heart of reciprocal regulation of E-cadherin- and integrin-mediated adhesions via signaling modulation. Developmental Cell, 15(4), pp. 494-496. (doi: 10.1016/j.devcel.2008.09.016) (PMID:18854134)

Huser, C. , Heath, V., Pringle, M.-A. , Bell, A.K., Crighton, D., Ryan, K. , Inman, G. , Stein, T. and Gusterson, B. (2008) TSC22 in Mammary Gland Development and Breast Cancer. Breast Cancer Research 2008, London, UK, 13 May 2008. (doi: 10.1186/bcr1901)

2005

Inman, G. J. (2005) Linking Smads and transcriptional activation. Biochemical Journal, 388, E1. (doi: 10.1042/BJ20042133) (PMID:15702493) (PMCID:PMC1134782)

2002

Inman, G. J. , Nicolas, F. J. and Hill, C. S. (2002) Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity. Molecular Cell, 10(2), pp. 283-294. (PMID:12191474)

Inman, G. J. , Nicolas, F. J., Callahan, J. F., Harling, J. D., Gaster, L. M., Reith, A. D., Laping, N. J. and Hill, C. S. (2002) SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Molecular Pharmacology, 62(1), pp. 65-74. (doi: 10.1124/mol.62.1.65) (PMID:12065756)

Howell, M., Inman, G. J. and Hill, C. S. (2002) A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3) cooperates with XFast-1 in regulating gastrulation movements. Development, 129(12), pp. 2823-2834. (PMID:12050132)

Inman, G. J. and Hill, C. S. (2002) Stoichiometry of active Smad-transcription factor complexes on DNA. Journal of Biological Chemistry, 277(52), pp. 51008-51016. (doi: 10.1074/jbc.m208532200) (PMID:12374795)

Randall, R. A., Germain, S., Inman, G. J. , Bates, P. A. and Hill, C. S. (2002) Different Smad2 partners bind a common hydrophobic pocket in Smad2 via a defined proline-rich motif. EMBO Journal, 21, pp. 145-156. (doi: 10.1093/emboj/21.1.145) (PMID:11782434) (PMCID:PMC125817)

2001

Inman, G. J. , Binne, U. K., Parker, G. A., Farrell, P. J. and Allday, M. J. (2001) Activators of the Epstein-Barr virus lytic program concomitantly induce apoptosis, but lytic gene expression protects from cell death. Journal of Virology, 75(5), pp. 2400-2410. (doi: 10.1128/JVI.75.5.2400-2410.2001) (PMID:11160743) (PMCID:PMC114823)

2000

Inman, G. J. and Allday, M. J. (2000) Apoptosis induced by TGF- 1 in Burkitt's lymphoma cells is caspase 8 dependent but is death receptor independent. Journal of Immunology, 165(5), pp. 2500-2510. (doi: 10.4049/jimmunol.165.5.2500) (PMID:10946276)

Inman, G. J. and Allday, M. J. (2000) Resistance to TGF-β1 correlates with a reduction of TGF-β type II receptor expression in Burkitt’s lymphoma and Epstein–Barr virus-transformed B lymphoblastoid cell lines. Journal of General Virology, 81(6), pp. 1567-1578. (doi: 10.1099/0022-1317-81-6-1567) (PMID:10811940)

1998

Srivastava, S. et al. (1998) Novel anchorage of GluR2/3 to the Postsynaptic Density by the AMPA Receptor–Binding Protein ABP. Neuron, 21(3), pp. 581-591. (doi: 10.1016/S0896-6273(00)80568-1) (PMID:9768844)

Osten, P. et al. (1998) The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and α- and β-SNAPs. Neuron, 21(1), pp. 99-110. (doi: 10.1016/s0896-6273(00)80518-8) (PMID:9697855)

1995

Allday, M.J., Inman, G.J. , Crawford, D.H. and Farrell, P.J. (1995) DNA damage in human B cells can induce apoptosis, proceeding from G1/S when p53 is transactivation competent and G2/M when it is transactivation defective. EMBO Journal, 14(20), pp. 4994-5005. (doi: 10.1002/j.1460-2075.1995.tb00182.x) (PMID:7588628) (PMCID:PMC394603)

Inman, G. J. and Farrell, P. J. (1995) Epstein--Barr virus EBNA-LP and transcription regulation properties of pRB, p107 and p53 in transfection assays. Journal of General Virology, 76(9), pp. 2141-2149. (doi: 10.1099/0022-1317-76-9-2141) (PMID:7561751)

1993

Inman, G.J. , Cook, I.D. and Lau, R.K.W. (1993) Human papillomaviruses, tumour suppressor genes and cervical cancer. International Journal of STD and AIDS, 4(3), pp. 128-134. (doi: 10.1177/095646249300400302) (PMID:8391853)

1992

Allan, G. J., Inman, G. J. , Parker, B. D., Rowe, D. T. and Farrell, P. J. (1992) Cell growth effects of Epstein-Barr virus leader protein. Journal of General Virology, 73(6), pp. 1547-1551. (doi: 10.1099/0022-1317-73-6-1547) (PMID:1318948)

1991

Megson, A., Inman, G. J. , Hunt, P. D., Baylis, H. A. and Hall, R. (1991) The gene for apocytochrome B of Theileria annulata resides on a small linear extrachromosomal element. Molecular and Biochemical Parasitology, 48(1), pp. 113-115. (doi: 10.1016/0166-6851(91)90171-2) (PMID:1779987)

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