HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer.

plays an important role in cell survival or tumor progression. For these reasons, is an emerging therapeutic target in cancer development. Here we report that Hduanyu18425 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through alteration of lysosomal activity. Hduanyu18425 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression. However, NTS-induced MUL1/MULAN/GIDE/MAPL (mitochondrial ubiquitin ligase activator of NFKB 1) leads to downregulation of Hduanyu18425 via K48-linked ubiquitination at the lysine 446 (K446) residue. MUL1 knockdown hinders NTS-induced lysosome inhibition or cytotoxicity through the reduction of Hduanyu18425 ubiquitination in HNC cells. While MUL1 was suppressed, Hduanyu18425 was overexpressed in tissues of HNC patients. NTS strongly inhibited HNC progression via alterations of expression of MUL1 and in vivo in a xenograft model. However, NTS did not induce inhibition of tumor progression or Hduanyu18425 reduction in MUL1 knockout (KO) HNC cells which were generated by CRISPR/Cas9 system. The data provide compelling evidence to support the idea that the regulation of the axis can be a novel strategy for the treatment of HNC.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}