In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter.

Monitoring of exosome dynamics in living organisms is essential to demonstrate the real functions of cancer-derived exosomes. Currently, these have been elucidated in vitro or under non-physiological conditions in vivo in most cases. To overcome these limitations, we developed an imaging method using Antares2-mediated bioluminescence resonance energy transfer (BRET) for observing long-term accumulation of exosomes in vivo.

Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC), characterized by decreased expression of hormone receptors and human epidermal growth factor type 2 receptor, has poor prognosis and lacks effective therapeutics. Recently, the mTOR inhibitor rapamycin and its analogs have attracted growing interests and evaluated as therapeutic agents against TNBC, in which the PI3K/AKT/mTOR pathway is often activated. However, some TNBCs are less sensitive to these drugs.

c-Src promotes tumor progression through downregulation of microRNA-129-1-3p.

MicroRNAs (miRNAs) fine-tune cellular signaling by regulating expression of signaling proteins, and aberrant expression of miRNAs is observed in many cancers. The tyrosine kinase c-Src is upregulated in various human cancers, but the molecular mechanisms underlying c-Src-mediated tumor progression remain unclear. In previous investigations of miRNA-mediated control of c-Src-related oncogenic pathways, we identified miRNAs that were downregulated in association with c-Src transformation and uncovered the signaling networks by predicting their target genes, which might act cooperatively to control tumor progression.

Src in endosomal membranes promotes exosome secretion and tumor progression.

c-Src is a membrane-associated tyrosine kinase that has key roles in the signaling transduction that controls cell growth, adhesion, and migration. In the early stage of carcinogenesis, c-Src is activated under the plasma membrane and transduces oncogenic signals. Here we show that c-Src localized to the endosomal membrane has unique functions in c-Src-transformed cells.

Sensitive and rapid quantification of exosomes by fusing luciferase to exosome marker proteins.

Exosomes have emerged as important mediators of intercellular communication. Although their modes of action have been elucidated, the molecular mechanisms underlying their secretion, sorting of molecules, uptake into recipient cells, and biological distribution in vivo remain elusive. Here, we present a novel system for quantifying secreted exosomes by introducing ectopic or CRISPR/Cas9-mediated knock-in of luciferase-fusion exosome markers such as CD63.

MicroRNA-137-mediated Src oncogenic signaling promotes cancer progression.

The tyrosine kinase c-Src is frequently overexpressed and activated in a wide variety of human cancers. However, the molecular mechanisms responsible for the upregulation of c-Src remain elusive. To examine whether microRNA-mediated c-Src upregulation promotes cancer progression, we screened miRNAs with complementarity to the 3'-UTR of c-Src mRNA.

Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.

Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers.