18 January 2015 3 5K Report

We are interested in the dynamics of quiescent and proliferative cancer stem cells (CSCs) when tumor tissue shows invasion. We have previously investigated into the expression level of CD44 variant 8-10 (CD44v8-10), one of the reliable cancer stem cell markers, in parallel with proto-oncogenic molecule c-Myc, the expression of which is supported by redox stress-induced Wnt/beta-catenin signal pathway. CD44v8-10-positive cancer cells are enriched at the invasive front of the gastric and breast cancer. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 (high)/ Fbw7 (high)/ c-Myc (low) and proliferative cancer stem-like cells with CD44v8-10 (high)/ Fbw7 (low)/ c-Myc (high). The heterogeneity of E3-ubiquitin ligase Fbw7 expression in a cancer cell-autonomous manner is responsible for the co-existence of quiescent and proliferative CSCs at the invasive front (Biochem Biophys Res Commun. 2014 Jan 10;443(2):622-7.).

Furthermore, metastatic potential of B16F1 melanoma cells in Mx1-Cre Fbxw7Δ/Δ mice has recently suggested that Fbw7 ablation in bone marrow-derived stromal cells (BMSCs) induced accumulation of Notch intracellular domain and consequent transcriptional activation of Ccl2. Fbw7-deficient mice exhibited increased serum levels of the chemokine CCL2, thereby promoting metastatic tumor growth. Fbw7 expression in peripheral blood was associated with serum CCL2 concentration and disease prognosis of human breast cancer patients (J Clin Invest. 2015 Jan 2. pii: 78782.).

To be sure, Nakayama K, et al emphasized that Fbw7 antagonizes tumor invasion in not only a cell-autonomous manner, but also a non-cell-autonomous manner in terms of Fbw7/Notch/CCL2 axis,

I wonder whether or not Fbw7 expression changees at the invasive front is regulated in a cancer cell-autonomous or non-cell-autonomous manner in terms of oxidative stress and canonical Wnt signal. Furthermore, CSCs are really enriched at the invasive front in the heterogeneous manner of the G0 and Galert phase?

I would appreciate if you would give your opinion and perspective.

http://www.ncbi.nlm.nih.gov/pubmed/25555218

http://www.ncbi.nlm.nih.gov/pubmed/24333422

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