The silencing of GFAT reduced CD44<sup>high</sup>/CD24<sup>low</sup> cancer stem cell (CSC)-like subpopulations, aldehyde dehydrogenase-positive cell populations, and mammosphere size, which were further diminished by gene targeting of Has2.
We will critically assess the multilayered regulation of HAS2, the most critical hyaluronan synthase, and its role in cancer growth, metabolism, and therapy.
Notably, HAS2 loss- and gain-of-function experiments revealed that it regulates CRC malignancy through TGF-β expression and SMAD2/Snail downstream components.
Importantly, high levels of USP17 and HAS2 were detected in a panel of cancer cell lines compared to normal cells, and immunohistochemical stainings revealed higher expression of USP17 and HAS2 in tissues of lung cancer patients compared to normal tissue.
Aberrant expression of the human hyaluronan synthase 2 (HAS2) gene has been implicated in the pathology of malignancy, pulmonary arterial hypertension, osteoarthritis, asthma, thyroid dysfunction, and large organ fibrosis.