Aki Manninen

Aki Manninen


Prof. of Cell Biology at the Faculty of Biochemistry and Molecular Medicine, Coordinator of Virus Core Laboratory at Biocenter Oulu
Molecular Cell Biology

48 peer reviewed publications in international journals. The publications have been cited 1770 times, of which the most cited publication accounts for 195 citations. The author has a h-index of 23.00. (WoS)


Specific integrin functions in prostate cancer
A laminin-rich basement membrane orients the polarity of epithelial cells by serving as a ligand for members of the integrin family of ECM receptors. How the different integrins convey signals from the ECM into the cells is not thoroughly understood. Integrin-mediated signalling is perturbed in many different cancer types contributing to abnormal migration, invasion, proliferation and survival of tumour cells. Epithelial polarity is a critical regulator of oncogenesis and multiple polarity-related genes appear to function as tumour suppressors. In this project we study functional synergies or antagonisms between selected integrins in prostate cancer. 3D cultures of genetically engineered prostate epithelial cell lines as well as primary prostate organoids are used as a model system. Lentiviral vectors are used to overexpress (oncogenes) or knock out (CRISPR) selected prostate cancer associated genes. Our aim is to facilitate the development of novel targeted therapeutic approaches to inhibit malignant transformation by modulating reciprocal signalling between prostate cancer cells and their tumour-promoting microenvironment.

Research interests

  • Epithelial polarity, prostate cancer, integrins, extracellular matrix
  • CRISPR/Cas, RNAi, prostate organoid technology, 3D cultures

Publications in peer-reviewed journals


Myllymäki SM, Liu X, Varjosalo M, and Manninen A (2021). Proximity-Dependent Biotinylation (BioID) of Integrin Interaction Partners. Methods Mol. Biol. 2217, 57-69.


Hujaya SD, Manninen A, Kling K, Wagner JB, Vainio SJ, Liimatainen H (2019) Self-assembled nanofibrils from RGD-functionalized cellulose nanocrystals to improve the performance of PEI/DNA polyplexes. J Colloid Interface Sci. 553:71-82.

Myllymäki SM, Manninen A (2019) Cell surface expression of integrin β4-subunit in the absence of α6-subunit. ScienceMatters doi: 10.19185/matters.201902000007

Zhang K, Manninen A (2019) 3D cell culture models of epithelial tissues. Methods Mol Biol. 1926: 77-84.

Pitkäaho T, Manninen A, Naughton TJ (2019) Focus prediction in digital holographic microscopy using deep convolutional neural networks. Appl Opt 58 (5), A202-A208

Kozlova N, Mennerich D, Samoylenko A, Dimova EY, Koivunen P, Biterova E, Richter K, Hassinen A, Kellokumpu S, Manninen A, Miinalainen I, Glumoff V, Ruddock L, Drobot L, Kietzmann T (2019) The pro-oncogenic adaptor CIN85 inhibits hypoxia-inducible factor prolyl hydroxylase-2. Cancer Res. 79: 4042-4056.

Myllymäki SM, Kämäräinen UR, Liu X, Cruz SP, Miettinen S, Vuorela M, Varjosalo, M, Manninen A (2019). Assembly of the β4-integrin interactome based on proximal biotinylation in the presence and absence of heterodimerization. MCP. 18:277-293.


Nair RR, Koivisto H, Jokivarsi K, Miinalainen IJ, Autio KJ, Manninen A, Tanila H, Hiltunen JK, Kastaniotis AJ (2018) Impaired mitochondrial fatty acid synthesis leads to neurodegeneration in mice. J Neurosci. 38(45):9781-9800.

Paakkola T, Salokas K, Miinalainen I, Lehtonen S, Manninen A, Kaakinen M, Ruddock LW, Varjosalo M, Kaarteenaho R, Uusimaa J, Hinttala R. (2018) Biallelic mutations in human NHLRC2 enhance myofibroblast differentiation in FINCA disease. Hum Mol Genet. 27: 4288-4302.

Gao P, Xia JH, Sipeky C, Dong XM, Zhang Q, Yang Y, Zhang P, Cruz SP, Zhang K, Zhu J, Lee HM, Suleman S, Giannareas N, Liu S, The PRACTICAL consortium, Tammela TLJ, Auvinen A, Wang X, Huang Q, Wang L, Manninen A, Vaarala MH, Wang L, Schleutker J, Wei GH (2018) Biology and clinical implications of the 19q13 aggressive prostate cancer susceptibility locus. Cell, 174:576-589.

Raykhel I, Moafi F, Myllymäki SM, Greciano PG, Matlin KS, Moyano JV, Manninen A*, Myllyharju J* (2018) Bambi is a novel HIF1-dependent modulator of TGFβ-mediated disruption of cell polarity in hypoxia. J Cell Sci  131 doi: 10.1242/jcs.210906. *equal contribution

Uusimaa J, Kaarteenaho R, Paakkola T, Tuominen H, Karjalainen MK, Nadaf J, Varilo T, Uusi- Mäkelä M, Suo-Palosaari M, Ilkka Pietilä I, Hiltunen AE, Ruddock L, Alanen H, Biterova E, Miinalainen I, Salminen A, Soininen R, Manninen A, Sormunen R, Kaakinen M, Vuolteenaho R, Herva R, Vieira P,Dunder T, Kokkonen H,Moilanen JS, Rantala H, Nogee LM, Majewski J, Rämet M, Hallman M,Hinttala R (2018) NHLRC2 variants identified in patients with Fibrosis, Neurodegeneration, and Leptomeningeal Angiomatosis (FINLA) - Characterization of a novel  cerebropulmonary disease. Acta Neuropathologica, 135: 727-742.


Zhang K, Myllymäki SM, Gao P, Devarajan R, Kytölä V, Nykter M, Wei GH, Manninen A (2017) Oncogenic K-Ras upregulates ITGA6-expression via FOSL1 to induce anoikis resistance and synergizes with αV-class integrins to promote EMT. Oncogene, 36: 5681-5694.

Matlin KS, Myllymäki SM, Manninen A. (2017) Laminins in Epithelial Cell Polarization - Old Questions in Search of New Answers. Cold Spring Harbor Perspectives in Biology, 9: a027920.

Moilanen J, Löffek S, Kokkonen N, Salo S, Väyrynen J, Hurskainen T, Manninen A, Riihilä P, Heljasvaara R, Franzke CW, Kähäri VM, Salo T, Mäkinen M, Tasanen K (2017). Significant role of collagen XVII and integrin β4 in migration and invasion of the less aggressive squamous cell carcinoma cells. Scientific Reports, 7:45057.

Manninen A, Varjosalo M (2017) A proteomics view on integrin-mediated adhesions. Proteomics, 17: p.201600022.


Zhang K, Lee HM, Wei GH, Manninen A (2016) Meta-analysis of gene expression and integrin-associated signaling pathways in papillary renal cell carcinoma subtypes. Oncotarget, 7: 84178-84189


Manninen A (2015) Epithelial polarity - Generating and integrating signals from the ECM with integrins. Exp Cell Res. 334: 337-349

Cattavarayane S, Palovuori R, Jayendrakishore TR, Manninen A. (2015) α6β1- and αV-integrins are required for long-term self-renewal of murine embryonic stem cells in the absence of LIF. BMC Cell Biol. :3

Carrera M, Bitu CC, de Oliveira CE, Cervigne NK, Graner E, Manninen A, Salo T, Coletta RD. (2015) HOXA10 controls proliferation, migration and invasion in oral squamous cell carcinoma. Int J Clin Exp Pathol. 8(4):3613-23


Junttila S, Saarela U, Halt K, Manninen A, Pärssinen H, Lecca RM, Brandli AW, Sims-Lucas S, Skovorodkin I, Vainio SJ. (2014) Functional genetic targeting of the embryonic kidney progenitor cells ex vivo. J. Am. Soc. Nephrol. 26(5):1126-37.

Huang Q, Whitington T, Gao P, Lindberg JF, Yuehong Yang Y,Sun J, Väisänen MR, Szulkin R,Annala M, Yan J, Egevad LA, Zhang K, Lin R, Jolma A, Nykter M, Manninen A, Wiklund F, Vaarala MH, Visakorpi T, Xu J, Taipale J, Wei GH. (2014) A prostate cancer susceptibility allele at 6q22 increases RFX6 expression by modulating HOXB13 chromatin binding. Nature Genetics 46:126–135.


Teräväinen TP, Myllymäki SM, Friedrichs J, Strohmeyer N, Moyano JV, Wu C, Matlin KS, Muller DJ, Manninen A. (2013) αV-integrins are required for mechanotransduction in MDCK epithelial cells. PLoS ONE, 8(8):e71485.

Rilla K, Pasonen-Seppänen S, Kärnä R, Karjalainen H, Törrönen K, Koistinen V, Tammi MI, Tammi RH, Teräväinen T, Manninen A. (2012) HAS3-induced accumulation of hyaluronan in 3D MDCK cultures results in mitotic spindle misorientation and disturbed organization of epithelium.

Greciano PG, Moyano JV, Buschmann MM, Tang J, Lu Y, Rudnicki J, Manninen A, Matlin KS. (2012) Laminin 511 Partners with Laminin 332 to Mediate Directional Migration of Madin-Darby Canine Kidney (MDCK) Epithelial Cells. Mol Biol Cell. 23(1):121-36.

Veikkolainen V, Naillat F, Railo A, Chi L, Manninen A, Hohenstein P, Hastie N, Vainio S, Elenius K. (2012) ErbB4 signaling regulates cell division and polarization during kidney epithelial development. J. Am. Soc. Nephrol. 23(1):112-22.

de Oliveira JT, de Matos AJ, Santos AL, Pinto R, Gomes J, Hespanhol V, Chammas R, Manninen A, Bernardes ES, Reis CA, Rutteman G, Gärtner F. (2011) Sialylation regulates galectin-3/ligand interplay during mammary tumour progression: a case of targeted uncloaking Int. J. Dev. Biol. 55(7-8-9):823-834.

Myllymäki SM, Teräväinen TP, Manninen A. (2011) Two Distinct Integrin-Mediated Mechanisms Contribute to Apical Lumen Formation in Epithelial Cells. PLoS ONE 6(5): e19453.

Moilanen AM, Rysä J, Mustonen E, Serpi R, Aro J, Tokola H, Leskinen H, Manninen A, Levijoki J, Vuolteenaho O, Ruskoaho H. (2011) Intramyocardial BNP Gene Delivery Improves Cardiac Function Through Distinct Context-Dependent Mechanisms. Circ Heart Fail. 4:483-95.

de Oliveira JT, de Matos AJ, Gomes J, Vilanova M, Hespanhol V, Manninen A, Rutteman G, Chammas R, Gärtner F, Bernardes ES. (2010) Coordinated expression of galectin-3 and galectin-3-binding sites in malignant mammary tumours: implications for tumour metastasis. Glycobiology, 20:1341-52.

Friedrichs J, Manninen A, Muller DJ, Helenius J. (2008) Galectin-3 regulates integrin α2β1-mediated adhesion to collagen-I and ­IV.  J. Biol. Chem. 283: 32264-72.

Arpiainen S, Järvenpää S-M, Manninen A, Viitala P, Lang MA, Pelkonen O, Hakkola J. (2008) Coactivator PGC-1 regulates the fasting inducible xenobiotic-metabolizing enzyme CYP2A5 in mouse primary hepatocytes. Toxicol. Appl. Pharm. 232:135-41.

Torkko JM, Manninen A, Schuck S, Simons K. (2008) Depletion of apical transport proteins perturbs epithelial cyst formation and ciliogenesis. J. Cell Sci. 121:1193-203.

Friedrichs J, Torkko JM, Helenius J, Teräväinen TP, Fullekrug J, Muller DJ, Simons K, Manninen A. (2007) Contributions of galectin-3 and -9 to epithelial cell adhesion analysed by single cell force spectroscopy. J. Biol. Chem. 282: 29375-83.

Schuck S, Gerl MJ, Ang A, Manninen A, Keller P, Mellman I, Simons K. (2007) Rab10 is involved in basolateral transport in polarized Madin-Darby canine kidney cells. Traffic 8:47-60.

Manninen A, Verkade P, Le Lay S, Torkko J, Kasper M, Fullekrug J, Simons K. (2005) Caveolin-1 is not essential for biosynthetic apical membrane transport. Mol. Cell. Biol. 25:10087-10096.

Vieira O, Verkade P, Manninen A, Simons K. (2005) FAPP2 is involved in the transport of apical cargo in polarized MDCK cells. J. Cell. Biol. 170:521-526.

Delacour D, Gouyer V, Zanetta J-P, Drobecq H, Leteurtre E, Grard G, Moreau-Hannedouche O, Maes E, Pons A, Andre S, Le Bivic A, Gabius HJ, Manninen A, Simons K, Huet G. (2005) Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells. J. Cell. Biol. 169:491-501.

Schuck S*, Manninen A*, Honsho M, Fullekrug J, Simons K. (2004) Generation of single and double knockdowns in polarized epithelial cells by retrovirus-mediated RNA interference. Proc. Natl. Acad. Sci. USA 101:4912-4917.*equal contribution.

Sillanpaa N, Magureanu CG, Murumagi A, Reinikainen A, West A, Manninen A, Lahti M, Ranki A, Saksela K, Krohn K, Lahesmaa R, Peterson P. (2004) Autoimmune regulator induced changes in the gene expression profile of human monocyte-dendritic cell-lineage. Mol Immunol 41(12):1185-98

Lahti AL, Manninen A, Saksela K. (2003) Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB. Virology 310(1):190-6

Manninen A., Saksela K. (2002) HIV-1 Nef interacts with IP3R to activate calcium signaling in T cells. J Exp Med 195(8):1023-32

Hiipakka, M., Huotari, P., Manninen, A., Renkema, G.H., and Saksela, K. (2001) Inhibition of cellular functions of HIV-1 Nef by artificial SH3 domains. Virology 286: 152-9

Manninen A., Huotari P., Hiipakka M,. Renkema G-H., Saksela K. (2001) Activation of NFAT-dependent gene expression by Nef: conservation among divergent Nef alleles, dependence on SH3-binding and membrane association, and cooperation with protein kinase C-q. J Virol 75 (6): 3034-3037

Renkema G-H., Manninen A., Saksela K. (2001) Human immunodeficiency virus type-1 Nef selectively associates with a catalytically active subpopulation of p21-activated kinase 2 (PAK2) independently of PAK2 binding to Nck or b-PIX. J Virol 75 (5): 2154-2160

Manninen A., Renkema G-H., Saksela K. (2000) Synergistic activation of NFAT by HIV-1 Nef and the Ras/MAPK pathway. J Biol Chem 275 (22): 16513-16517

Renkema G-H., Manninen A., Mann D.A., Harris M., Saksela K. (1999) Identification of the Nef-associated kinase as p21-activated kinase 2. Curr Biol 9: 1407-1410

Manninen A., Hiipakka M., Vihinen M., Lu W., Mayer B., Saksela K. (1998) SH3-domain binding function of HIV-1 Nef is required for association with a PAK-related kinase. Virology 250: 273-282

Thesis supervisions

Ph.D Thesis supervision
  • Satu-Marja Myllymäki (Ph.D.) 1.10.2015

  • Sandhanakrishnan Cattavarayane (Ph.D.) 13.5.2016

  • Kai Zhang (Ph.D.) 16.6.2017