<i>14-3-3σ</i>Functions as an Intestinal Tumor Suppressor

Winter, Markus; Rokavec, Matjaž; Hermeking, Heiko

doi:10.1158/0008-5472.can-20-4192

Cited by 9 publications

(11 citation statements)

References 53 publications

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“…It is well known that 14-3-3σ, one member of the 14-3-3 protein family, is crucial for nuclear signals by changing the subcellular localization of many of its binding partners, regulating signal transduction, apoptosis, checkpoint control, and nutrient sensing [29][30][31] . By phosphorylating amino acid motifs, 14-3-3 protein can also act as a lipid raft protein, targeting intracellular proteins and stimulating their translocation [32][33][34] .…”

Section: Lplunc1 Enhances the Nuclear Translocation Of Phb1 In Npc Cellsmentioning

confidence: 99%

LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1‐p53/c‐Myc axis

et al. 2022

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Cancer cells usually prefer glycolysis to support their proliferation. Our previous studies have shown that the long palate, lung, and nasal epithelial cell clone 1 (LPLUNC1) can up-regulate prohibitin 1 (PHB1) expression to inhibit the proliferation of nasopharyngeal carcinoma (NPC) cells. Given that PHB1 is an important regulator of cell energy metabolism, we explored whether and how LPLUNC1 regulated glucose glycolysis in NPC cells. LPLUNC1 or PHB1 over-expression decreased glycolysis and increased oxidative phosphorylation (OXPHOS)-related protein expression in NPC cells, accompanied by enhancing PHB1 and 14-3-3σ expression and promoting phosphorylated PHB1 nuclear translocation. Coimmunoprecipitation indicated that 14-3-3σ directly interacted with phosphorylated PHB1. PHB1 Y259A mutant over-expression abrogated the decreasing glycolysis and increasing OXPHOS-related protein expression induced by LPLUNC1 over-expression in NPC cells. LPLUNC1 over-expression also increased p53, but decreased c-Myc expression in NPC cells, which were crucial for the decrease in glycolysis and increase in OXPHOS-related protein expression induced by LPLUNC1 over-expression. Finally, we found that treatment with all-trans retinoic acid (ATRA) reduced the viability and clonogenicity of NPC cells, decreased glycolysis and increased OXPHOS-related protein xpression by enhancing LPLUNC1 expression in NPC cells. Therefore, the LPLUNC1-PHB1-p53/c-Myc axis decreased glycolysis in NPC cells and ATRA up-regulated LPLUNC1 expression, a promising drug for intervention of NPC.

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Section: Lplunc1 Enhances the Nuclear Translocation Of Phb1 In Npc Cellsmentioning

confidence: 99%

LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1‐p53/c‐Myc axis

et al. 2022

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“…For the generation of STAT3 and c-JUN expression signatures, we compiled RNA-Seq datasets from the NCBI Gene Expression Omnibus (GEO), as described recently 43 . Differentially regulated genes were identified using RNA-Seq data from cell lines/tissues with STAT3, c-JUN, or SRF ectopic expression or knockdown (KD)/knockout (KO).…”

Section: Methodsmentioning

confidence: 99%

“…Differential expression between tumors of different stages was calculated using one-way ANOVA with a post-test for linear trend from stage 1 to stage 4. Gene Set Enrichment Analysis (GSEA) of curated gene sets obtained from the Molecular Signatures database (MSigDB) 35 , or as indicated 43 , 49 , was performed on pre-ranked gene lists ordered by expression correlation coefficients (Pearson) with the Δ34a expression signature, mature miR-34a, or CSF1R expression, as described previously 21 . The significance of enrichments is presented by normalized enrichment scores (NES) and false discovery rate-adjusted q values.…”

Section: Methodsmentioning

confidence: 99%

Csf1r mediates enhancement of intestinal tumorigenesis caused by inactivation of Mir34a

Liu¹,

Bouznad²,

Kaller³

et al. 2022

Int. J. Biol. Sci.

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The CSF1 receptor (CSF1R) encoding mRNA represents a direct target of miR-34a. However, the in vivo relevance of the suppression of CSF1R by miR-34a for intestinal tumor suppression mediated by the p53/miR-34a pathway has remained unknown. Here, Apc Min/+ mice with intestinal-epithelial cell (IEC)-specific deletions of Mir34a showed increased formation of adenomas and decreased survival, whereas deletion of Csf1r decreased adenoma formation and increased survival. In adenomas deletion of Mir34a enhanced proliferation, STAT3 signaling, infiltration with fibroblasts, immune cells and microbes, and tumor stem cell abundance and decreased apoptosis. Deletion of Csf1r had the opposite effects. In addition, homeostasis of intestinal secretory and stem cells, and tumoroid formation were affected in opposite directions by deletion of Mir34a and CSF1R . Concomitant deletion of Csf1r and Mir34a neutralized the effects of the single deletions. mRNAs containing Mir34a seed-matching sites, which encode proteins related to EMT (epithelial-mesenchymal transition), stemness and Wnt signaling, were enriched after Mir34a inactivation in adenomas and derived tumoroids. Netrin-1/Ntn1 and Transgelin/Tagln were characterized as direct targets of Mir34a and Csf1r signaling. Mir34a -inactivation related expression signatures were associated with CMS4/CRISB+D, stage 4 CRCs and poor patient survival. In tumoroids the loss of Mir34a conferred resistance to 5-FU which was mediated by Csf1r . This study provides genetic evidence for a requirement of Mir34a-mediated Csf1r suppression for intestinal stem/secretory cell homeostasis and tumor suppression, and suggests that therapeutic targeting of CSF1R may be effective for the treatment of CRCs with defects in the p53/miR-34a pathway.

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“…14-3-3 σ, as a member of the highly conservative 14-3-3 protein family, mainly exists in epithelial cells and can promote G2-phase block of the cell cycle after DNA damage by interacting with a variety of signal proteins such as CDK2, CDC2, etc., and regulate cell growth, differentiation and proliferation in mammal cells [ 14 , 15 , 16 ]. It also acts as a key regulator of p53 to control mitotic progression in response to DNA damage and inhibits the development of several substantial tumors, such as nasopharyngeal, colorectal and breast cancers [ 17 , 18 , 19 , 20 , 21 ]. In some studies on lung and gastric cancers, 14-3-3σ was found to show high expression in cancer tissues, promoting the progression of tumorigenesis [ 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

J Subgroup Avian Leukosis Virus Strain Promotes Cell Proliferation by Negatively Regulating 14-3-3σ Expressions in Chicken Fibroblast Cells

Wang

Sun

et al. 2023

Viruses

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This study focuses on clarifying the regulation of chicken 14-3-3σ protein on the fibrous histiocyte proliferation caused by ALV-J-SD1005 strain infection. DF-1 cells were inoculated with 102 TCID50 of ALV-J-SD1005 strain; the cell proliferation viability was dramatically increased and 14-3-3σ expressions were dramatically decreased within 48 hours after inoculation. Chicken 14-3-3σ over-expression could significantly decrease the cell proliferation and the ratio of S-phase cells, but increase the ratio of G2/M-phase cells in ALV-J-infected DF-1 cells; by contrast, chicken 14-3-3σ knockdown expression could cause the opposite effects. Additionally, chicken 14-3-3σ over-expression could also dramatically down-regulate the expressions of CDK2/CDC2, but up-regulate p53 expressions in the DF-1 cells; in contrast, the knockdown expression could significantly increase the expressions of CDK2/CDC2 and decrease p53 expressions. It can be concluded that chicken 14-3-3σ can inhibit cell proliferation and cell cycle by regulating CDK2/CDC2/p53 expressions in ALV-J-infected DF1 cells. ALV-J-SD1005 strain can promote cell proliferation by reducing 14-3-3σ expressions. This study helps to clarify the forming mechanism of acute fibrosarcoma induced by ALV-J infection.

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14-3-3σFunctions as an Intestinal Tumor Suppressor

Cited by 9 publications

References 53 publications

LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1‐p53/c‐Myc axis

LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1‐p53/c‐Myc axis

Csf1r mediates enhancement of intestinal tumorigenesis caused by inactivation of Mir34a

J Subgroup Avian Leukosis Virus Strain Promotes Cell Proliferation by Negatively Regulating 14-3-3σ Expressions in Chicken Fibroblast Cells

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