In spite of the above limitations, a few biomarkers including the proliferation marker Ki-67 and genetic markers such as c-MYC and PTEN have consistently shown their independent prognostic impact both for biochemical recurrence and for clinical outcome parameters such as metastatic disease or prostate-specific mortality.
Here we demonstrate that PTEN plays an unexpected role in regulating its own stability through the transcriptional upregulation of the deubiquitinase USP11 by the PI3K/FOXO pathway, and further show that this feedforward mechanism is implicated in its tumor-suppressive role, as mice lacking Usp11 display increased susceptibility to PTEN-dependent tumor initiation, growth and metastasis.
Proportional hazard models were used to assess PTEN expression and its interaction with IGF-IR, in relation to lethal prostate cancer (cancer-specific death or distant metastases).
PTEN, a critical tumor and metastasis suppressor gene negatively regulates cell survival, proliferation, migration and angiogenesis via the PI3K/Akt pathway.
On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases.
Therefore, the mRNA expression of the four members of the HER family as well as the frequency of PTEN allelic loss and KRAS/BRAF mutations were determined in pretreatment biopsies from a series of 100 locally advanced rectal cancers and then their ability to predict distant metastases was evaluated.
Collectively, our data identified a tumor inducer, SYNJ2BP, which could activate the PI3K/AKT/GSK3β/SNAI1 signaling pathway through the lysosome-mediated degradation of PTEN, and promote both EMT and tumor metastasis during the progression of breast cancer.
Our findings demonstrate a remarkable plasticity of PTEN expression in metastatic tumour cells in response to different organ microenvironments, underpinning an essential role of co-evolution between the metastatic cells and their microenvironment during the adaptive metastatic outgrowth.
We have previously demonstrated a significant correlative relationship between PTEN deletion and ERG rearrangement, both in the development of clinically localized prostate cancers and metastases.
Taken together, these reaults suggest that the PTEN/FOXO3a/PLZF signalling pathway may be capable of inhibiting growth and metastasis in PC by regulating VEGF-mediated angiogenesis, which requires further in vivo and in vitro studies and can potentially be a therapeutic target for PC.