Hypoxia attenuates the proinflammatory response in colon cancer cells by regulating IκB

摘要: Two main features common to all solid tumors are tissue hypoxia and inflammation, both of which cause tumor progression, metastasis, therapy resistance increased mortality. Chronic inflammation is associated with cancer risk, as demonstrated for inflammatory bowel disease patients developing colon cancer. However, the interplay between on molecular level remains be elucidated. We found that MC-38 mouse cells contain functional hypoxic (HIF-1α) (p65/RelA) signaling pathways. In contrast myeloid lineage, HIF-1α levels remained unaffected in treated LPS, failed induce NF-κB. A similar regulation canonical HIF NF-κB target genes confirmed these results. RNA deep sequencing p65/RelA knock-down revealed a surprisingly large fraction required number proinflammatory regulation, respectively. Hypoxia attenuated response LPS by inhibiting nuclear translocation independently HIF-1α, was enhanced IκBα decreased IKKβ phosphorylation. These data demonstrate interaction pathways needs considered when designing therapies targeting or