Naa10p promotes cell invasiveness of esophageal cancer by coordinating the c-Myc and PAI1 regulatory axis

Cell Death Dis. 2022 Nov 24;13(11):995. doi: 10.1038/s41419-022-05441-0.

Abstract

N-α-acetyltransferase 10 protein, Naa10p, is involved in various cellular functions impacting tumor progression. Due to its capacity to acetylate a large spectrum of proteins, both oncogenic and tumor-suppressive roles of Naa10p have been documented. Here, we report an oncogenic role of Naa10p in promoting metastasis of esophageal cancer. NAA10 is more highly expressed in esophageal cancer tissues compared to normal tissues. Higher NAA10 expression also correlates with poorer survival of esophageal cancer patients. We found that NAA10 expression was transcriptionally regulated by the critical oncogene c-Myc in esophageal cancer. Furthermore, activation of the c-Myc-Naa10p axis resulted in upregulated cell invasiveness of esophageal cancer. This increased cell invasiveness was also elucidated to depend on the enzymatic activity of Naa10p. Moreover, Naa10p cooperated with Naa15p to interact with the protease inhibitor, PAI1, and prevent its secretion. This inhibition of PAI1 secretion may derive from the N-terminal acetylation effect of the Naa10p/Naa15p complex. Our results establish the significance of Naa10p in driving metastasis in esophageal cancer by coordinating the c-Myc-PAI1 axis, with implications for its potential use as a prognostic biomarker and therapeutic target for esophageal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / physiopathology
  • Humans
  • N-Terminal Acetyltransferase A / genetics
  • N-Terminal Acetyltransferase A / metabolism
  • N-Terminal Acetyltransferase E / genetics
  • N-Terminal Acetyltransferase E / metabolism

Substances

  • N-Terminal Acetyltransferase A
  • N-Terminal Acetyltransferase E
  • NAA10 protein, human
  • MYC protein, human
  • SERPINE1 protein, human