(A) In hepatocellular carcinoma (HCC), STAT3 activation is the driver of Rac1 activation. Elevated HCC cell CD147 expression leads to increased Src phosphorylation and activation, which consequently triggers STAT3 phosphorylation and activation. STAT3 stimulates the transcription of DOCK8, a known RacGEF, thereby stimulating Rac1 activation and promoting metastasis. (B) In contrast, Rac1 is the driver of STAT3 activation in HPV positive cervical cancer cells. The E6 viral protein activates Rac1 through an unknown mechanism, which results in NF-κB activation involving p65 phosphorylation and AKT. NF-κB drives the increase in expression of IL-6, resulting in autocrine activation of STAT3, which is required for the proliferation and survival of cervical cancer cells.