The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells

Abstract

Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44+ subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression.

Dynamic metabolic reprogramming in dendritic cells: an early response to influenza infection that is essential for effector function

“…Paradoxically, mice with l-MYC-deficient dendritic cells have reduced T cell response during either bacterial or viral infection [68, 69]. In this respect, while it is possible that our reagents were nonspecific we suggest that is unlikely for several reasons: the primers we used are specific for c-MYC [102], these primers only amplified one species, and the c-Myc antibodies we used detected a single band at the appropriate size. Moreover, we observed a transient increase in response to activation stimuli (i.e.…”

An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2

“…Samples were permeabilized with 0.4 M glycine and 0.3% Triton X-100, and nonspecific binding was blocked with 2% normal swine serum (Dako, Glostrup, Denmark). Staining was performed as described previously, 48 using the primary anti-SHH (Santa Cruz Biotechnology, SC-373779), PTCH1 (Abcam, ab53715), or SERPINB2 (Abcam, ab47742) antibody. Samples were examined by fluorescence microscopy (Zeiss LSM 510 Meta).…”

Aberrant regulation of Wnt signaling in hepatocellular carcinoma

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