In this signal loop, midkine is a mediator of ALK activation, and NF-κB is a major signal transducer that induces transcription of genes to facilitate anoikis resistance or proliferation, ultimately leading to protection from CTC death during circulation and promotion of subsequent tumor recurrence and metastasis, as demonstrated by the results from our animal studies and correlative studies in HCC patients. The gene discussed is ALK; the disease is hepatocellular carcinoma.