SIRT1 as a masterful reciprocal regulator of molecular mechanisms and signaling pathways involved in tumor growth and expansion

Abstract

Sirtuin 1, which is more commonly identified as SIRT1, is a well-recognized NAD⁺-dependent histone and/or protein deacetylase that operates a wide range of cellular and molecular mechanisms involved in carcinogenic processes. SIRT1 not only regulates the primary mechanisms involved in tumorigenesis but also is responsible for controlling other processes, such as cell migration and metastasis, autophagy, and apoptotic flux, as well as chemotherapeutic resistance. It is well established that SIRT1 works at the upstream of signal transduction pathways, such as p53 signaling, together with FOXO mechanism, as well as the others. Indeed, SIRT1 by its deacetylase activity deacetylates different molecules in those signaling pathways and mostly causes a kind of blockade in the signaling of interest. Nonetheless, many aspects of SIRT1-cancer relationship are ambiguous, and more experiments should be performed for further uncovering of the concept. In the current review, we first highlight the major regulators of SIRT1 in cancer and then underscore key signal transduction pathways regulated by SIRT1. In the following, the role of SIRT1 will be discussed in tumor progression, from tumorigenesis to chemotherapeutic resistance, and at last, the contribution of SIRT1 to human cancers will be exemplified by some studies conducted in the field.

Keywords: Carcinogenesis; Drug resistance; Neoplasm; Signal transduction; Sirtuin 1.

Fig. 1

Key targets modulated by SIRT1 in cancer

Fig. 2

Regulation of cancer-related signaling pathways can be mediated by SIRT1

Fig. 3

SIRT1 and cancer proliferation, metastasis, and autophagy