Effector

Protein kinase B

Biology

P70-S6 Kinase 1

Phosphorylation

Kinase

Mechanistic target of rapamycin

Ribosomal s6 kinase

Ribosomal protein s6

Signal transduction

Cell biology

mTORC1

Cancer research

Medicine

PI3K/AKT/mTOR pathway

Cancer Letters

p70 S6 kinase (p70S6K) is best known for its regulatory roles in protein synthesis and cell growth by phosphorylating its primary substrate, ribosomal protein S6, upon mitogen stimulation. The enhanced expression/activation of p70S6K has been correlated with poor prognosis in some cancer types, suggesting that it may serve as a biomarker for disease monitoring. p70S6K is a critical downstream effector of the oncogenic PI3K/Akt/mTOR pathway and its activation is tightly regulated by an ordered cascade of Ser/Thr phosphorylation events. Nonetheless, it should be noted that other upstream mechanisms regulating p70S6K at both the post-translational and post-transcriptional levels also exist. Activated p70S6K could promote various aspects of cancer progression such as epithelial-mesenchymal transition, cancer stemness and drug resistance. Importantly, novel evidence showing that p70S6K may also regulate different cellular components in the tumor microenvironment will be discussed. Therapeutic targeting of p70S6K alone or in combination with traditional chemotherapies or other microenvironmental-based drugs such as immunotherapy may represent promising approaches against cancers with aberrant p70S6K signaling. Currently, the only clinically available p70S6K inhibitors are rapamycin analogs (rapalogs) which target mTOR. However, there are emerging p70S6K-selective drugs which are going through active preclinical or clinical trial phases. Moreover, various screening strategies have been used for the discovery of novel p70S6K inhibitors, hence bringing new insights for p70S6K-targeted therapy.

p70 S6 kinase as a therapeutic target in cancers: More than just an mTOR effector