FBXL10 promotes ERRα protein stability and proliferation of breast cancer cells by enhancing the mono-ubiquitylation of ERRα

Yang, Yangyang; Li, Shujing; Li, Bowen; Li, Yanan; Xia, Kangkai; Aman, Sattout; Yang, Yanchun; Ahmad, Bashir; Zhao, Binggong; Wu, Harry X.

doi:10.1016/j.canlet.2021.01.007

Cited by 14 publications

(19 citation statements)

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“…FBXL10 has been reported to be overexpressed in gynecological tumors, but its role in tumorigenesis and progression was still controversial [ 41 , 43 , 44 ]. Kottakis et al and our previous research demonstrated that FBXL10 served as an oncogene to promote the self-renewal and proliferation of breast cancer cells via regulating multiple factors including miRNAs/PRC1/PRC2 axis and estrogen-related receptor α (ERRα)/peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1-β) signaling [ 43 , 44 ]. Additional, genomics functional screening found that FBXL10 was also associated with anti-estrogen resistance in breast cancer [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the JmjC and PHD domains of FBXL10 endow its demethylase activity to remove the H3K4me3 [ 37 ], H3K36me2 [ 38 ], and H3K79me2/3 [ 39 , 40 ]. Studies demonstrated that high expression of FBXL10 was detected in many types of tumors, and its oncogenic function was closely associated with high aggression of cancers and poor prognosis of patients [ 41 – 43 ]. It has been reported that FBXL10 was overexpressed in breast cancer, knockdown of FBXL10 induced cell cycle arrest, decreased cell proliferation and tumorigenesis [ 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

“…Studies demonstrated that high expression of FBXL10 was detected in many types of tumors, and its oncogenic function was closely associated with high aggression of cancers and poor prognosis of patients [ 41 – 43 ]. It has been reported that FBXL10 was overexpressed in breast cancer, knockdown of FBXL10 induced cell cycle arrest, decreased cell proliferation and tumorigenesis [ 43 , 44 ]. In contrast, another research found that FBXL10 served as a tumor suppressor via regulating the ribosome biogenesis [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

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FBXL10 promotes EMT and metastasis of breast cancer cells via regulating the acetylation and transcriptional activity of SNAI1

Yang

Zhao

et al. 2021

Cell Death Discov.

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F-box and leucine-rich repeat protein 10 (FBXL10) has been reported to play a regulatory role in the initiation and development of breast cancer. Bioinformatics analyses revealed that FBXL10 may involve in the process of cytoskeleton organization. This research aimed to investigate the function of FBXL10 in epithelial-mesenchymal transition (EMT) and metastasis of breast cancer, and tried to reveal the molecular mechanism involved in this issue. Functional experiments in vitro revealed that FBXL10 promoted the migration and invasion of breast cancer cells through inhibiting E-cadherin expression and inducing EMT. Mechanical studies revealed that FBXL10 could specifically interact with SNAI1, but not Slug or ZEB1. And it promoted the transcriptional repression activity of SNAI1 on CDH1 in breast cancer cells. Furthermore, FBXL10 had a positive role for the deacetylation of SNAI1 by facilitating the interaction between SNAI1 and HDAC1, a dominating deacetylase of SNAI1. And the deacetylated SNAI1 showed a more suppressive ability to inhibit the transcription of E-cadherin. Moreover, mouse models were also conducted to confirm the effect of FBXL10 on the lung metastasis of breast cancer in vivo. Totally, our data revealed that FBXL10 served as a pro-metastatic factor in breast cancer via repressing the expression of E-cadherin and inducing EMT. It may provide a novel regulatory axis in the EMT of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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FBXL10 promotes EMT and metastasis of breast cancer cells via regulating the acetylation and transcriptional activity of SNAI1

Yang

Zhao

et al. 2021

Cell Death Discov.

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“…Therefore, in-depth examination into the molecular mechanisms that affect the activity of ERRα could shed light on ERRα targets. For example, in a recent study, Yang et al ( 15 ) revealed that F-box and leucine-rich repeat protein 10 increased ERRα enrichment at the promoter region of its target genes by promoting the mono-ubiquitylation of ERRα. However, additional, novel pathogenesis mechanisms are yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…A number of orphan nuclear receptors are activated by the peroxisome proliferator-activated receptor γ (PPARγ) coactivator (PGC) family, including PGC-1α, PGC-1β and PRC ( 13 ). In the absence of specific ligands, ERRα can be activated by PGC-1 family members, such as PGC-1α ( 14 ) and PGC-1β ( 15 ). Moreover, as wild-type PGC-1α (PGC-1α WT) can activate other receptors, such as ERRβ and ERRγ, researchers have reported that some peptides (such as L3-09) can bind to ERRα specifically.…”

Section: Introductionmentioning

confidence: 99%

PI3K/AKT phosphorylation activates ERRα by upregulating PGC‑1α and PGC‑1β in gallbladder cancer

Wang

Jin

2021

Mol Med Rep

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The nuclear estrogen-related receptor-α (errα) is an orphan receptor that has been identified as a transcriptional factor. Peroxisome proliferator-activated receptor-γ (PParγ) coactivator-1-α (PGc-1α) and PParγ coactivator-1-β (PGc-1β) act as the co-activators of errα. our previous study reported that activated errα promoted the invasion and proliferation of gallbladder cancer cells by promoting Pi3K/aKT phosphorylation. Therefore, the aim of the current study was to investigate whether Pi3K/aKT phosphorylation could enhance errα activity in a positive feedback loop. lY294002 and insulin-like growth factor i (iGF-i) were used to inhibit and promote Pi3K/aKT phosphorylation, respectively. a 3X ere-TaTa luciferase reporter was used to measure errα activity. The present study found that lY294002 inhibited Pi3K/aKT phosphorylation, decreased the proliferation and invasion of noZ cells and suppressed the activity of errα. conversely, iGF-i induced Pi3K/aKT phosphorylation, promoted the proliferation and invasion of noZ cells and enhanced the activity of errα. The protein expression levels of PGc-1α and PGc-1β were elevated and reduced by iGF-i and lY294002, respectively. Moreover, knockdown of PGc-1α and PGc-1β antagonized errα activation, which was enhanced by Pi3K/aKT phosphorylation. Taken together, the present study demonstrated that Pi3K/aKT phosphorylation triggered errα by upregulating the expression levels of PGc-1α and PGc-1β in noZ cells.

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RBBP6‐Mediated ERRα Degradation Contributes to Mitochondrial Injury in Renal Tubular Cells in Diabetic Kidney Disease

Hu,

Chen

et al. 2024

Advanced Science

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Diabetic Kidney Disease (DKD), a major precursor to end‐stage renal disease, involves mitochondrial dysfunction in proximal renal tubular cells (PTCs), contributing to its pathogenesis. Estrogen‐related receptor α (ERRα) is essential for mitochondrial integrity in PTCs, yet its regulation in DKD is poorly understood. This study investigates ERRα expression and its regulatory mechanisms in DKD, assessing its therapeutic potential. Using genetic, biochemical, and cellular approaches, ERRα expression Was examined in human DKD specimens and DKD mouse models. We identified the E3 ubiquitin ligase retinoblastoma binding protein 6 (RBBP6) as a regulator of ERRα, promoting its degradation through K48‐linked polyubiquitination at the K100 residue. This degradation pathway significantly contributed to mitochondrial injury in PTCs of DKD models. Notably, conditional ERRα overexpression or RBBP6 inhibition markedly reduced mitochondrial damage in diabetic mice, highlighting ERRα’s protective role in maintaining mitochondrial integrity. The interaction between RBBP6 and ERRα opens new therapeutic avenues, suggesting that modulating RBBP6‐ERRα interactions could be a strategy for preserving mitochondrial function and slowing DKD progression.

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FBXL10 promotes ERRα protein stability and proliferation of breast cancer cells by enhancing the mono-ubiquitylation of ERRα

Cited by 14 publications

References 58 publications

FBXL10 promotes EMT and metastasis of breast cancer cells via regulating the acetylation and transcriptional activity of SNAI1

FBXL10 promotes EMT and metastasis of breast cancer cells via regulating the acetylation and transcriptional activity of SNAI1

PI3K/AKT phosphorylation activates ERRα by upregulating PGC‑1α and PGC‑1β in gallbladder cancer

RBBP6‐Mediated ERRα Degradation Contributes to Mitochondrial Injury in Renal Tubular Cells in Diabetic Kidney Disease

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