Hypoxic signaling in lymphatic colorectal cancer metastasis

Lymphatic metastasis is a clinicopathological hallmark of colorectal cancer (CRC), ultimately leading to patient mortality. At the molecular level, the colonic tumor microenvironment devolves onto an imbalance between oxygen supply and consumption, leading to hypoxia, an independent adverse prognostic factor in CRC and virtually all solid cancers. We hereby summarize hypoxia-sensitive molecular mechanisms promoting CRC lymphatic metastasis, emphasizing parallels between vascular and lymphatic processes, while contrasting lymphatic-specific pathways located downstream of the hypoxic signaling. Potential therapeutic approaches to alleviate intrametastatic hypoxic signaling improving CRC patient prognosis are also discussed.