NON-THEMATIC REVIEW Emerging role of nuclear protein 1 (NUPR1) in cancer biology Uttio Roy Chowdhury & Rajeev S. Samant & Oystein Fodstad & Lalita A. Shevde Published online: 20 January 2009 # Springer Science + Business Media, LLC 2009 Abstract NUPR1, or p8 or com1, was first identified from rat pancreas during acute pancreatitis and later as a gene whose expression was upregulated in metastatic breast cancer cells. NUPR1 is a molecule whose expres- sion is upregulated in response to stress and is hence influenced by the host microenvironment. While NUPR1 has been implicated in several diseases, there is no singular biochemical pathway that can be attributed to its role in cancer. NUPR1 has been found to aid the establishment of metastasis and to play a key role in the progression of several malignancies including those of breast, thyroid, brain and pancreas. NUPR1 has been implicated in inducing chemoresistance in pancreatic and breast cancer cells, protecting them from apoptosis and making tumor cells genetically unstable. In prostate cancer, however, NUPR1 appears to have tumor suppres- sive activity. Understanding the mechanism of action of the multifaceted functions of NUPR1 may open up new dimensions towards creating novel therapies against cancer as well as other pathologies. This review draws on several published studies on NUPR1, mainly in cancer biology, and assesses NUPR1 from the perspective of its functional role in making cancer cells resistant to the action of conventional chemotherapeutic drugs. Keywords NUPR1 . p8 . com-1 . Stress . Cell cycle . Cancer . Hypertrophy Abbreviations NUPR1 Nuclear protein 1 NLS Nuclear localization signal NES Nuclear export signal MEF Mouse embryonic fibroblasts Nuclear protein 1 (NUPR1) was originally identified as p8 [1], a gene that was preferentially upregulated in response to cellular stress during the acute phase of pancreatitis in rat. Shortly after, the group of Ree et al independently identified a novel candidate of metastasis-1 (com-1) gene, that was significantly upregulated in the metastases formed in the central nervous system upon injection of cancer cells originally isolated from micrometastases in the bone marrow of a breast cancer patient [2]. It was postulated that com-1 participates in intracellular signaling that facilitates tumor establishments in a secondary organ [2]. Subsequently it was found that com-1 was the human counterpart of the rat p8 described earlier [1]. NUPR1 has been implicated in a wide range of biological functions which are context-dependent and sometimes contradictory and difficult to explain. Various reports have shown NUPR1 to be both inducer and suppressor of cell and tumor growth and is also associated with chemoresistance in pancreatic [3] and breast cancer [4]. While NUPR1 expression enhances growth of HeLa cells [5] and protects liver cells from LPS and CCl 4 -induced injuries [6, 7], it also contributes to adriamycin-induced apoptosis [8]. In the light of several disjunct pieces of evidence, clearly NUPR1 presents itself as an interesting small molecule with varied biological functions. The aim of this review is to bring Cancer Metastasis Rev (2009) 28:225–232 DOI 10.1007/s10555-009-9183-x U. R. Chowdhury : R. S. Samant : O. Fodstad : L. A. Shevde (*) Mitchell Cancer Institute, University of South Alabama, MCI 3018, 1660 Springhill Avenue, Mobile, AL 36604, USA e-mail: lsamant@usouthal.edu O. Fodstad Norwegian Radium Hospital Rikshospitalet University Hospital, Faculty Division, Norwegian Radium Hospital, Oslo, Norway