Interplay of Developmental Hippo-Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer

被引:14
作者
Mourkioti, Ioanna [1 ]
Angelopoulou, Andriani [1 ]
Belogiannis, Konstantinos [1 ]
Lagopati, Nefeli [1 ,2 ]
Potamianos, Spyridon [3 ]
Kyrodimos, Efthymios [3 ]
Gorgoulis, Vassilis [1 ,2 ,4 ,5 ,6 ,7 ]
Papaspyropoulos, Angelos [1 ,2 ]
机构
[1] Natl Kapodistrian Univ Athens NKUA, Med Sch, Dept Histol & Embryol, Mol Carcinogenesis Grp, Athens 11527, Greece
[2] Acad Athens, Biomed Res Fdn, Athens 11527, Greece
[3] Univ Athens, Hippocrat Hosp, ENT Dept 1, Athens 11527, Greece
[4] Univ Dundee, Med Sch, Clin Mol Pathol, Dundee DD1 9SY, Scotland
[5] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Canc Res Ctr, Mol & Clin Canc Sci, Manchester M20 4GJ, Lancs, England
[6] Natl & Kapodistrian Univ Athens, Med Sch, Ctr New Biotechnol & Precis Med, Athens 11527, Greece
[7] Univ Surrey, Fac Hlth & Med Sci, Surrey GU2 7YH, England
关键词
prostate cancer; DNA damage response (DDR); Hippo pathway; Notch pathway; interplay; THERAPEUTIC TARGETS; INDUCED SENESCENCE; DOWN-REGULATION; P53; MUTATIONS; UP-REGULATION; REPAIR; INHIBITION; CELLS; ERG; METASTASIS;
D O I
10.3390/cells11152449
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Prostate cancer belongs in the class of hormone-dependent cancers, representing a major cause of cancer incidence in men worldwide. Since upon disease onset almost all prostate cancers are androgen-dependent and require active androgen receptor (AR) signaling for their survival, the primary treatment approach has for decades relied on inhibition of the AR pathway via androgen deprivation therapy (ADT). However, following this line of treatment, cancer cell pools often become resistant to therapy, contributing to disease progression towards the significantly more aggressive castration-resistant prostate cancer (CRPC) form, characterized by poor prognosis. It is, therefore, of critical importance to elucidate the molecular mechanisms and signaling pathways underlying the progression of early-stage prostate cancer towards CRPC. In this review, we aim to shed light on the role of major signaling pathways including the DNA damage response (DDR) and the developmental Hippo and Notch pathways in prostate tumorigenesis. We recapitulate key evidence demonstrating the crosstalk of those pathways as well as with pivotal prostate cancer-related 'hubs' such as AR signaling, and evaluate the clinical impact of those interactions. Moreover, we attempt to identify molecules of the complex DDR-Hippo-Notch interplay comprising potentially novel therapeutic targets in the battle against prostate tumorigenesis.
引用
收藏
页数:20
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