A paradoxical role for sestrin 2 protein in tumor suppression and tumorigenesis

Abstract

Sestrin 2, a highly conserved stress-induced protein, participates in the pathological processes of metabolic and age-related diseases. This p53-inducible protein also regulates cell growth and metabolism, which is closely related to malignant tumorigenesis. Sestrin 2 was reported to regulate various cellular processes, such as tumor cell proliferation, invasion and metastasis, apoptosis, anoikis resistance, and drug resistance. Although sestrin 2 is associated with colorectal, lung, liver, and other cancers, sestrin 2 expression varies among different types of cancer, and the effects and mechanisms of action of this protein are also different. Sestrin 2 was considered a tumor suppressor gene in most studies, whereas conflicting reports considered sestrin 2 an oncogene. Thus, this review aims to examine the literature regarding sestrin 2 in various cancers, summarize its roles in suppression and tumorigenesis, discuss potential mechanisms in the regulation of cancer, and provide a basis for follow-up research and potential cancer treatment development.

Keywords: Cancer; Sestrin 2; Tumor suppressor; Tumorigenesis.

Fig. 1

A schematic diagram showing the structure and transcription regulators of sestrin 2. A The functional domains of human sestrin 2 (sestrin-A, sestrin-B, and sestrin-C). In sestrin-A, the cysteine residue (C125) and conserved residues of the proton relay system (Y127 and H132) are important for its antioxidant activity. In sestrin-C, the two surface-exposed aspartates (D406 and D407, DD motif) are responsible for interacting with GATOR2 to inhibit mTORC1 signaling. B Sestrin2 expression plays a central role in cancer regulated by multiple transcription factors and miRNAs

Fig. 2

Pathways of sestrin 2-mediated suppression of different cancers by inhibiting cell proliferation, migration, and invasion and inducing apoptosis

Fig. 3

Pathways involved in sestrin 2-mediated promotion of autophagy in different cancers

Fig. 4

Pathways of sestrin 2 in different cancers that promote anoikis resistance, cell growth, and drug resistance

Fig. 5

Sestrin 2 pathways that mediate cancer cell survival under stress conditions