Emerging therapeutic strategies for Wnt-dependent colon cancer targeting macropinocytosis.

Aberrations in the Wnt signaling pathway, particularly mutations in genes like APC and β-catenin, are pivotal in initiating and driving the progression of colorectal cancer (CRC), establishing this pathway as a crucial target for therapeutic intervention. Membrane trafficking plays a key role in regulating Wnt signaling by controlling the activation, modulation, and secretion of essential signaling molecules that contribute to CRC progression. This review explores the connection between membrane trafficking and Wnt signaling, with a specific focus on macropinocytosis-an endocytic process involved in nutrient uptake that also plays a role in Wnt signal regulation.

Na,K-ATPase activity promotes macropinocytosis in colon cancer via Wnt signaling.

Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the β-catenin destruction complex inside multivesicular bodies (MVBs) and lysosomes. In this study, we introduce Ouabain, an inhibitor of the Na,K-ATPase pump that establishes electric potentials across membranes, as a potent inhibitor of Wnt signaling. We find that Na,K-ATPase levels are elevated in advanced colon carcinoma, that this enzyme is elevated in cancer cells with constitutively activated Wnt pathway and is activated by GSK3 inhibitors that increase macropinocytosis.

The PMA phorbol ester tumor promoter increases canonical Wnt signaling via macropinocytosis.

Activation of the Wnt pathway lies at the core of many human cancers. Wnt and macropinocytosis are often active in the same processes, and understanding how Wnt signaling and membrane trafficking cooperate should improve our understanding of embryonic development and cancer. Here, we show that a macropinocytosis activator, the tumor promoter phorbol 12-myristate 13-acetate (PMA), enhances Wnt signaling.

Addition of exogenous diacylglycerol enhances Wnt/β-catenin signaling through stimulation of macropinocytosis.

Activation of Wnt signaling triggers macropinocytosis and drives many tumors. We now report that the exogenous addition of the second messenger lipid sn-1,2 DAG to the culture medium rapidly induces macropinocytosis. This is accompanied by potentiation of the effects of added Wnt3a recombinant protein or the glycogen synthase kinase 3 (GSK3) inhibitor lithium chloride (LiCl, which mimics Wnt signaling) in luciferase transcriptional reporter assays.

Multifractality in Surface Potential for Cancer Diagnosis.

Recent advances in high-resolution biomedical imaging have improved cancer diagnosis, focusing on morphological, electrical, and biochemical properties of cells and tissues, scaling from cell clusters down to the molecular level. Multiscale imaging revealed high complexity that requires advanced data processing methods of multifractal analysis. We performed label-free multiscale imaging of surface potential variations in human ovarian cancer cells using Kelvin probe force microscopy (KPFM).

The PMA Phorbol Ester Tumor Promoter Increases Canonical Wnt Signaling Via Macropinocytosis.

Activation of the Wnt pathway lies at the core of many human cancers. Wnt and macropinocytosis are often active in the same processes, and understanding how Wnt signaling and membrane trafficking cooperate should improve our understanding of embryonic development and cancer. Here we show that a macropinocytosis activator, the tumor promoter Phorbol 12-myristate 13-acetate (PMA), enhances Wnt signaling.

Evaluation of digestion methods for analysis of trace metals in mammalian tissues and NIST 1577c.

Digestion techniques for ICP analysis have been poorly studied for biological samples. This report describes an optimized method for analysis of trace metals that can be used across a variety of sample types. Digestion methods were tested and optimized with the analysis of trace metals in cancerous as compared to normal tissue as the end goal.