The role of NUPR1 in response to stress and cancer development

Toxicol Appl Pharmacol. 2022 Nov 1:454:116244. doi: 10.1016/j.taap.2022.116244. Epub 2022 Sep 15.


Stress contributes to the development of many human diseases, including cancer. Based on the source of stress, it can be divided into external stress, such as environmental carcinogens, chemicals, and radiation, and internal stress, like endoplasmic reticulum (ER) stress, hypoxia, and oxidative stress. Nuclear Protein 1 (NUPR1, p8 or Com-1) is a small, highly basic transcriptional regulator that participates in regulating a variety of cellular processes including DNA repair, ER stress, oxidative stress response, cell cycle, autophagy, apoptosis, ferroptosis and chromatin remodeling. A large number of studies have reported that NUPR1 expression can be stimulated rapidly in response to various stresses. Thus, NUPR1 is also known as a stress-response gene. Since the role of NUPR1 in breast cancer was identified in 1999, an increasing number of studies sought to reveal its function in cancer. High expression of NUPR1 has been identified in oral squamous cell carcinoma, breast cancer, lung cancer, multiple myeloma, liver cancer and renal cancer. In this review, we summarize current studies of NUPR1 in response to multiple external stressors and internal stressors, and its role in mediating stressors to cause different cell signaling responses. In addition, this review discusses the function of NUPR1 in carcinogenesis, tumorigenesis, metastasis, and cancer therapy. Thus, this review gives a comprehensive insight into the role of NUPR1 in mediating signals from stress to different cell responses, and this process plays a role in the development of cancer.

Keywords: Cancer; Environmental stress; External stress; Internal stress; NUPR1.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Breast Neoplasms* / genetics
  • Carcinogens, Environmental*
  • Carcinoma, Squamous Cell*
  • Female
  • Humans
  • Mouth Neoplasms*
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins


  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinogens, Environmental
  • Neoplasm Proteins
  • Nuclear Proteins