Table 2 Impact of the AKT isoforms on survival, therapy response and metastasis. Shows the impact of AKT isoform expression, phosphorylation and mutation on clinical parameters, namely overall survival, therapy response and metastasis. For more detailed information about the used predictors for therapy response see the corresponding section above. The effects are classified by the revealing studies. If the effect is restricted to a subtype of breast cancer, this is shown in the brackets. Also, additional information is mentioned in the brackets
From: Distinct functions of AKT isoforms in breast cancer: a comprehensive review
author | Ref. | effect |
|---|---|---|
Riggio et al. 2017 | [127] | high AKT2 âž” reduced overall survival |
Liu et al. 2012 | [224] | high pAKT1 âž” reduced overall and disease-free survival (association with Skp2 expression) |
Li et al. 2016 | [170] | high AKT1 âž” improved overall survival low AKT1 and high Twist âž” association with EMT high AKT3 âž” association with EMT |
Spears et al. 2012 | [195] | high pAKT1 âž” reduced overall survival and reduced metastasis-free survival high pAKT2 âž” reduced overall survival and reduced metastasis-free survival (ER-) |
Perez-Tenorio et al. 2014 | [101] | high AKT1 âž” poor prognosis (ER+) high AKT2 or AKT3 âž” poor prognosis (ER-) |
O’Hurley et al. 2014 | [100] | AKT3 amplification ➔ recurrence-free survival (ER+) and reduced metastasis-free survival (TNBC) |
Grell et al. 2012 | [201] | high AKT2 âž” improved response to trastuzumab (HER2+, metastatic) |
Kirkegaard et al. 2005 | [81] | high AKT2 âž” improved response to tamoxifen (ER+) |
Jordan et al. 2004 | [225] | high pAKT1 âž” reduced response to tamoxifen (ER+ cell line) |
Faridi et al. 2003 | [153] | high AKT3 âž” reduced response to tamoxifen (ER+ cell line) |
Knuefermann et al. 2003 | [227] | high pAKT1 âž” reduced response to paclitaxel, doxorubicin, 5-fluorouracil, etoposide, camptothecin (ER+ cell line) |
Liang et al. 2006 | [226] | high AKT1 and pAKT1 âž” reduced response to paclitaxel, doxorubicin, gemcitabine (cell lines) |
Sokolosky et al. 2011 | [228] | high activated AKT1 âž” reduced response to doxorubicin, etoposide, tamoxifen & improved response to mTOR inhibitor rapamycin (ER+ cell line) |
Steelman et al. 2011 | [162] | high activated AKT1 âž” reduced response to doxorubicin and tamoxifen (ER+ cell line) |
Taylor et al. 2011 | [229] | high activated AKT1 in combination with ERK activation âž” reduced response to doxorubicin and tamoxifen (ER+ cell line) |
Thirumurthi et al. 2014 | [142] | destabilization of SIRT6 by AKT1 âž” reduced response to tamoxifen (HER2+ cell line) |
Aktas et al. 2009 | [207] | high AKT2 in blood as predictor for presence of CTCs âž” reduced therapy response in general (metastatic breast cancer) |
Liu et al. 2006 | [129] | low AKT1 âž” reduced metastasis-free survival (combinatory with low TSC2) |
Cheng et al. 2007 | [164] | high AKT2 and high Twist âž” association with late stage and invasiveness of tumor |
Iliopoulos et al. 2009 | [163] | low AKT1/AKT2 ratio âž” increased metastasis |
van Agthoven et al. 2009 | [198] | high AKT2 âž” improved metastasis-free survival (ER+) |
Hohensee et al. 2017 | [171] | high AKT1 activity through loss of PTEN âž” reduced overall survival in brain metastasized breast cancer |