Nuclear PI3K signaling in cell growth and tumorigenesis

Abstract

The PI3K/Akt signaling pathway is a major driving force in a variety of cellular functions. Dysregulation of this pathway has been implicated in many human diseases including cancer. While the activity of the cytoplasmic PI3K/Akt pathway has been extensively studied, the functions of these molecules and their effector proteins within the nucleus are poorly understood. Harboring key cellular processes such as DNA replication and repair as well as nascent messenger RNA transcription, the nucleus provides a unique compartmental environment for protein–protein and protein–DNA/RNA interactions required for cell survival, growth, and proliferation. Here we summarize recent advances made toward elucidating the nuclear PI3K/Akt signaling cascade and its key components within the nucleus as they pertain to cell growth and tumorigenesis. This review covers the spatial and temporal localization of the major nuclear kinases having PI3K activities and the counteracting phosphatases as well as the role of nuclear PI3K/Akt signaling in mRNA processing and exportation, DNA replication and repair, ribosome biogenesis, cell survival, and tumorigenesis.

Molecular mechanisms of cholangiocarcinoma cell inhibition by medicinal plants

“…We hypothesized that the anti-proliferative effect of PEf occurs via the inhibition of Akt activation. Akt is a protein kinase that promotes cell growth and survival (35), and our previous study demonstrated that Akt is involved in the regulation of CCA cell proliferation and invasion (36). The results of the present study are concordant with another previous study, which demonstrated that Phyllanthus extracts inhibit prostate cancer cell proliferation by inhibiting Akt activation (37).…”

Effect of PI3K-mediated autophagy in human osteosarcoma MG63 cells on sensitivity to chemotherapy with cisplatin

“…Molecular signaling pathway of phosphatidylinositol 3-kinase (PI3K) is involved in regulation of cell proliferation, apoptosis, relapse and metastasis etc. In addition, PI3K/Akt plays an important role in tumor cell proliferation, apoptosis, autophagy, relapse and metastasis as well as degradation * 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 of extracellular matrix etc [9] . Interference of abnormal activation of PI3K/Akt can facilitate programmed cell death, thus inhibiting the tumor growth.…”

Nicotine-Induced Airway Smooth Muscle Cell Proliferation Involves TRPC6-Dependent Calcium Influx Via α7 nAChR

“…Dysfunction of the PI3K/Akt signaling pathway has been implicated in many human diseases, including COPD [22, 23]. In addition, various calcium-dependent signaling cascades are directly or indirectly influenced by the PI3K/Akt signaling pathway [22] via kinases and phosphatases.…”

“…In addition, various calcium-dependent signaling cascades are directly or indirectly influenced by the PI3K/Akt signaling pathway [22] via kinases and phosphatases. We previously showed that nicotine can induce activation of the Akt signaling pathway in RASMCs [8].…”