Sestrin2 Protein Positively Regulates AKT Enzyme Signaling and Survival in Human Squamous Cell Carcinoma and Melanoma Cells

Abstract

Background:The role of Sestrin2 (Sesn2) in skin squamous cell carcinoma (SCC) and melanoma is unknown. Results: Sesn2 increases AKT activation and resistance to UVB and chemotherapeutics and is up-regulated in SCC and melanoma. Conclusion: Sesn2 promotes AKT activation and survival of SCC and melanoma cells. Significance: Sesn2 may promote tumorigenesis and chemoresistance of SCC and melanoma.

The Expression of the Endogenous mTORC1 Inhibitor Sestrin 2 Is Induced by UVB and Balanced with the Expression Level of Sestrin 1

“…The finding that, different from the effects of individual gene knockdown (Fig 2), SESN1 and SESN2 were upregulated in parallel by UVB (Fig 4) might indicate that, under conditions of severe UVB stress, both SESNs are needed to assure an appropriate stress-response. The UVB-inducible expression of SESN2 in this study is in line with previous reports on SESN2 expression in keratinocyte cell lines and primary skin cells [32, 41]. Recently, SESN2 was reported to be upregulated by UVB, but also by UVA, in melanocytes [42].…”

“…However, the roles of endogenous mTOR regulators of the SESN family in the skin have been only incompletely studied so far. SESN2 was recently implicated in the UV responses of skin cells and in the suppression of tumorigenesis [32], yet the control of its expression has remained unknown.…”

Nck1 deficiency improves pancreatic β cell survival to diabetes-relevant stresses by modulating PERK activation and signaling

“…6B). As Sens2, through inhibiting mTORC1 or regulating PTEN, was reported to promote Akt activation [53,54], we determined that silencing Nck1 in MIN6 cells resulted in increased Akt activation (Fig. 6C, pAktThr 308 ).…”

NF-κB Signaling Activation Induced by Chloroquine Requires Autophagosome, p62 Protein, and c-Jun N-terminal Kinase (JNK) Signaling and Promotes Tumor Cell Resistance

“…Lentivirus was produced by co-transfection into HEK-293T cells (human embryonic kidney cells) with lentiviral constructs together with the pCMVdelta8.2 packaging plasmid and pVSV-G envelope plasmid using GenJet TM Plus DNA In Vitro Transfection Reagent (Signagen, Ijamsville, MD, as described previously (44,52). Virus-containing supernatants were collected 24 -48 h after transfection and used to infect recipients.…”

“…The threshold cycle number (CQ) for each sample was determined in triplicate. The CQ for values for HIF-1A, IL-8, BCL-2, BCL-XL, and p62 were normalized against GAPDH or ␤-actin as described previously (7,44,52). Amplification primers were as follows: 5Ј-GTT TAC TAA AGG ACA AGT CAC C-3Ј (forward) and 5Ј-TTC TGT TTG TTG AAG GGA G-3Ј (reverse) for the HIF-1A gene; 5Ј-ATG ACT TCC AAG CTG GCC GTG GCT-3Ј (forward) and 5Ј-TCT CAG CCC TCT TCA AAA ACT TCT-3Ј (reverse) for the human IL-8 gene; 5Ј-CAG AGA AGC CCA TGG ACA G-3Ј (forward) and 5Ј-AGC TGC CTT GTA CCC ACA TC-3Ј (reverse) for the human p62 gene; 5Ј-GTG GAT GAC TGA GTA CCT GAA C-3Ј (forward) and 5Ј-GCC AGG AGA AAT CAA ACA GAG G-3Ј (reverse) for BCL-2 gene; 5Ј-GAC ATC CCA GCT CCA CAT C-3Ј (forward) and 5Ј-GTT CCC ATA GAG TTC CAC AAA AG-3Ј (reverse) for BCL-XL gene; 5Ј-ATC GGA ACG GTG AAG GTG ACA-3Ј (forward) and 5Ј-ATG GCA AGG GAC TTC CTG TAA C-3Ј (reverse) for the human ␤-actin gene; and 5Ј-ACC ACA GTC CAT GCC ATC AC-3Ј (forward) and 5Ј-TCC ACC ACC CTG TTG CTG TA-3Ј (reverse) for the human GAPDH gene.…”