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. 2019 Nov 21;17:154. doi: 10.1186/s12964-019-0450-3

Table 1.

shows essential AKT isoform-specific effects in breast cancer in vitro and in vivo classified by the revealing study and the three AKT isoforms AKT1, AKT2 and AKT3

Author Ref. AKT1 AKT2 AKT3
Hutchinson et al. 2004 [125] tumor growth & proliferation ↑ (Rb, cyclin D1); metastasis ↓
Dillon et al. 2009 [123] tumor growth ↑; metastasis ↓ (ER) tumor growth Ø; metastasis & invasion ↑
Maroulakou et al. 2007 [124] tumor growth & proliferation ↑ (Cyclin D1, Rb); apoptosis ↓; invasion ↓; metastasis ↑ tumor growth ↓ (Cyclin D1, Rb); metastasis ↑ tumor growth Ø metastasis Ø
Riggio et al. 2017 [127] proliferation & tumor growth ↑ (Cyclin D1, S6); invasion & metastasis ↓ (integrin ß1, FAK, MMP9); migration Ø proliferation ↓; tumor growth Ø; migration & invasion & metastasis ↑ (F-actin, vimentin)
Liu et al. 2006 [129] proliferation & tumor growth ↑; migration & invasion ↓ (TSC2, Rho)
Grabinski et al. 2014 [130] proliferation ↓ proliferation ↓ proliferation ↓
Toulany et al. 2017 [131] proliferation & tumor growth ↑ (DNA-PKcs) proliferation Ø; tumor growth ↓ proliferation & tumor growth ↑ (DNA-PKcs)
Park et al. 2001 [59] colony formation Ø; invasion & metastasis ↑ (MMP-2)
Stottrup et al. 2016 [132] spheroid growth ↑ spheroid growth Ø spheroid growth ↑; invasion ↑ (N-cadherin)
Chin et al. 2014

[133]

[151]

proliferation ↑; spheroid formation ↑; migration ↓ proliferation ↑; spheroid formation ↑; maintaining spheroid architecture ↑; migration ↑ proliferation ↑; spheroid formation ↑; tumor growth ↑ (p27); spheroid growth ↑; migration ↓
Yang et al. 2011 [126] proliferation ↓ (Raf/MEK/ERK); migration ↓ proliferation ↓ (p27, CDK2); migration ↓
Ju et al. 2007 [136] proliferation & tumor growth ↑ (p21, p27, Cyclin D1); migration & metastasis ↑ (TSC2, F-actin, MIPγ, SDF-1, CXCL-16, paxillin and ezrin-radixin-moesin); angiogenesis ↓
Santi and Lee 2011 [128] proliferation ↑ proliferation ↑ (CDK2, Cyclin D, p27); mitochondrial autophagy ↓ (PGC1, p70S6K) proliferation ↑
Wang et al. 2008 [137] proliferation ↑; migration & chemotaxis ↑ (PKCζ, LIMK/Cofilin, integrin ß1)
Zhang et al. 2017 [138] proliferation & tumor growth ↑; apoptosis ↓; migration & invasion ↑ (miR-200c)
Polytarchou et al. 2011 [139] tumor growth Ø tumor growth ↑ (NFKB, CREB, miR-21, PTEN, PDCD4, Sprouty1)
Ye et al. 2016 [140] proliferation & tumor growth ↑; migration & invasion & chemotaxis ↑ (WDR26, PI3Kβ, Gβγ)
Yu et al. 2014 [141] apoptosis ↓ (p53, miR-17/20)
Thirumurthi et al. 2014 [142] tumor growth ↑ (SIRT6)

Plo et al. 2008

Baek et al. 2018

[143]

[121]

tumor growth & genomic instability (BRCA1, RAD51)
Ooms et al. 2015 [144] proliferation & tumor growth ↑; apoptosis ↓; migration & invasion & chemotaxis & metastasis ↓ (PIPP)
Zhang et al. 2016 [145] proliferation & tumor growth ↑ migration & invasion ↓ (miR-409-3p)
Yang et al. 2009 [146] apoptosis ↓; tumor growth ↑; invasion & metastasis ↑ (Par1)
Watson and Moorehead 2013 [147] proliferation & tumor growth ↑; metastasis Ø proliferation & tumor growth ↑; metastasis Ø
Irie et al. 2005 [148]

migration ↓ (ERK, E-cadherin, N-cadherin);

proliferation ↑

migration ↑ (vimentin); proliferation ↑
Gargini et al. 2015 [149] proliferation ↑; apoptosis ↓ (FoxO3, Bim); mammosphere growth ↓ (Bim, E cadherin, vimentin, ß-catenin, integrin β1) proliferation ↑; mammosphere growth ↓
Hu et al. 2018 [155] proliferation ↑; apoptosis ↓ (miR-433, Bcl-2, BAX)
Li et al. 2017 [156] proliferation & tumor growth ↑ apoptosis ↓ (p53, p21, p27, CyclinD1, Bcl2, XIAP); migration & invasion ↑ (miR-29b); angiogenesis ↑ (VEGF, c-myc)
Suyama et al. 2018 [96] AKT3-S472: proliferation & tumor growth ↓; apoptosis ↑ (Bim, MAPK/ERK, BAX); metastasis ↓
Lehman et al. 2012 [157] invasion ↑ (RhoC GTPase) invasion ↑ proliferation ↑; apoptosis ↓
Li et al. 2018 [113] invasion ↓ (ERK, ß-catenin)
Chung et al 2013 [154] proliferation Ø; migration & invasion ↓ (N-cadherin)
Chin and Toker 2010, 2014

[158]

[159]

[160]

migration ↓ (palladin)
Yoeli-Lerner et al. 2009, 2005

[112]

[161]

migration ↓ (GSK3, HDM2, NFAT1)
Choi et al. 2016 [152] migration & invasion ↓ (TIS21, Sp1, NOX4, mDia1/2/3) migration & invasion Ø
Iliopoulos et al. 2009 [163] TGF-β stimulated migration & metastasis ↓ (miR-200, Zeb1/2, E-cadherin); spheroid formation ↓ migration & metastasis Ø; spheroid formation Ø
Cheng et al. 2007, 2008

[164]

[168]

migration & invasion ↑ (Twist)
Leal-Orta et al. 2018 [165] migration & invasion ↑
Marcial-Medina et al. 2019 [166] migration ↑
Arboleda et al. 2003 [167] invasion Ø invasion & metastasis ↑ (integrin β1); post invasion survival ↑ invasion Ø
Li et al. 2016 [170] migration & invasion & metastasis ↓ (Twist1)
Hohensee et al 2016 [171] migration & invasion ↑; brain metastasis ↑
Grottke et al. 2016 [150] proliferation Ø; migration & chemotaxis Ø proliferation Ø; migration & chemotaxis Ø proliferation Ø; migration & chemotaxis & metastasis ↓ (S100A4, NFAT5)

Symbols have the following meanings: ↑ = increased, ↓ = decreased, Ø = no effect. Affected proteins and pathways are mentioned in the brackets