In non-small cell lung cancer, hyaluronan promotes the CD44-dependent association of the stem cell marker NANOG with U-STAT3, resulting in chemo-resistance that depends upon induced expression of the microRNA miR-21,[66] which indicated the NANOG/U-STAT3 signaling specific mechanism involved in miR-21 production is significant for the formation of future intervention strategies in the treatment of CD44-activated head and neck squamous cell carcinoma and reversing drug resistance during chemotherapy. Here, STAT3 is linked to head and neck squamous cell carcinoma.