Combined whole-organ imaging at single-cell resolution and immunohistochemical analysis of prostate cancer and its liver and brain metastases.

Early steps of cancer initiation and metastasis, while critical for understanding disease mechanisms, are difficult to visualize and study. Here, we describe an approach to study the processes of initiation, progression, and metastasis of prostate cancer (PC) in a genetically engineered RapidCaP mouse model, which combines whole-organ imaging by serial two-photon tomography (STPT) and post hoc thick-section immunofluorescent (IF) analysis. STPT enables the detection of single tumor-initiating cells within the entire prostate, and consequent IF analysis reveals a transition from normal to transformed epithelial tissue and cell escape from the tumor focus.

PTEN: Bridging Endocytosis and Signaling.

The transduction of signals in the PTEN/PI3-kinase (PI3K) pathway is built around a phosphoinositide (PIP) lipid messenger, phosphatidylinositol trisphosphate, PI(3,4,5)P or PIP Another, more ancient role of this family of messengers is the control of endocytosis, where a handful of separate PIPs act like postal codes. Prominent among them is PI(3)P, which helps to ensure that endocytic vesicles, their cargo, and membranes themselves reach their correct destinations. Traditionally, the cancer and the endocytic functions of the PI3K signaling pathway have been studied by cancer and membrane biologists, respectively, with some notable but overall minimal overlap.

Mitochondrial Complex I Inhibitors Expose a Vulnerability for Selective Killing of Pten-Null Cells.

A hallmark of advanced prostate cancer (PC) is the concomitant loss of PTEN and p53 function. To selectively eliminate such cells, we screened cytotoxic compounds on Pten;Trp53 fibroblasts and their Pten-WT reference. Highly selective killing of Pten-null cells can be achieved by deguelin, a natural insecticide.