Skp2 Regulates Subcellular Localization of PPARγ by MEK Signaling Pathways in Human Breast Cancer

Cheng, Hongge; Meng, Jie; Wang, Guisheng; Meng, Yuming; Liu, Yu; Dong, Wei; Fu, Chunyun; Deng, Kaifeng; Shen, Aiguo; Wang, Huimin; Dai, Shengming

doi:10.3390/ijms140816554

Cited by 13 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…leprae recognition with excess of free mannose inhibited PPARγ activation. PPARγ is a master transcriptional factor regulating multiple cellular functions, including lipid metabolism and foam-cell generation [ 54 – 57 ]. The role of PPARγ and subsequent lipid-droplet biogenesis in mycobacterium-infected macrophages has also been described [ 37 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves

et al. 2018

View full text Add to dashboard Cite

Mycobacterium leprae, an obligate intracellular bacillus, infects Schwann cells (SCs), leading to peripheral nerve damage, the most severe leprosy symptom. In the present study, we revisited the involvement of phenolic glycolipid I (PGL I), an abundant, private, surface M. leprae molecule, in M. leprae-SC interaction by using a recombinant strain of M. bovis BCG engineered to express this glycolipid. We demonstrate that PGL I is essential for bacterial adhesion and SC internalization. We also show that live mycobacterium-producing PGL I induces the expression of the endocytic mannose receptor (MR/CD206) in infected cells in a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent manner. Of note, blocking mannose recognition decreased bacterial entry and survival, pointing to a role for this alternative recognition pathway in bacterial pathogenesis in the nerve. Moreover, an active crosstalk between CD206 and the nuclear receptor PPARγ was detected that led to the induction of lipid droplets (LDs) formation and prostaglandin E2 (PGE2), previously described as fundamental players in bacterial pathogenesis. Finally, this pathway was shown to induce IL-8 secretion. Altogether, our study provides evidence that the entry of live M. leprae through PGL I recognition modulates the SC phenotype, favoring intracellular bacterial persistence with the concomitant secretion of inflammatory mediators that may ultimately be involved in neuroinflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In addition, it was demonstrated that casein-kinase-II-dependent phosphorylation of PPARγ leads to subcellular translocation of PPARγ from cytoplasm to nucleus regulated by CRM1 and that urokinasetype plasminogen activator promoted atherogenesis in hepatocytes by downregulating PON1 gene expression via PPARγ nuclear export mechanism [9,40]. Intracellular distribution of PPARγ was observed in BC tissues and cell lines [41], suggesting that poorly differentiated samples and highly invasive cell lines displayed mainly cytoplasmic PPARγ expression. Moreover, cytoplasmic localization of PPARγ was described as being mediated by Skp2 upon MEK1-dependent mechanism indicating cytoplasmic translocation of PPARγ promoted tumorigenesis in BC.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic PPARγ is a marker of poor prognosis in patients with Cox-1 negative primary breast cancers

Shao¹,

Kühn²,

Mayr

et al. 2020

J Transl Med

View full text Add to dashboard Cite

Background: The aim of this study was to investigate the expression of the nuclear receptor PPARγ, together with that of the cyclooxygenases Cox-1 and Cox-2, in breast cancer (BC) tissues and to correlate the data with several clinicobiological parameters including patient survival. Methods: In a well characterized cohort of 308 primary BC, PPARγ, Cox-1 and Cox-2 cytoplasmic and nuclear expression were evaluated by immunohistochemistry. Correlations with clinicopathological and aggressiveness features were analyzed, as well as survival using Kaplan-Meier analysis. Results: PPARγ was expressed in almost 58% of the samples with a predominant cytoplasmic location. Cox-1 and Cox-2 were exclusively cytoplasmic. Cytoplasmic PPARγ was inversely correlated with nuclear PPARγ and ER expression, but positively with Cox-1, Cox-2, and other high-risk markers of BC, e.g. HER2, CD133, and N-cadherin. Overall survival analysis demonstrated that cytoplasmic PPARγ had a strong correlation with poor survival in the whole cohort, and even stronger in the subgroup of patients with no Cox-1 expression where cytoplasmic PPARγ expression appeared as an independent marker of poor prognosis. In support of this cross-talk between PPARγ and Cox-1, we found that Cox-1 became a marker of good prognosis only when cytoplasmic PPARγ was expressed at high levels. Conclusion: Altogether, these data suggest that the relative expression of cytoplasmic PPARγ and Cox-1 may play an important role in oncogenesis and could be defined as a potential prognosis marker to identify specific high risk BC subgroups.

show abstract

“…Interestingly, MEK1 was recently described to have important roles in T cell transcriptional responses through regulation of the nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone (SMRT) at the promoter of c-Fos (39). In addition, there have been reports describing the interactions between PPAR-γ and the activation of MEK1/2-ERK1/2 (40), and MEK1 itself can play a role in regulating nuclear localization and activation of PPAR-γ (41)(42)(43). PPARs have important roles in regulating macrophage responses to inflammation (44,45), and represents one of likely many potential mechanisms by which MEK1/2-ERK1/2 regulates macrophage responses.…”

Section: ) Erk1mentioning

confidence: 99%

MEK1 regulates pulmonary macrophage inflammatory responses and resolution of acute lung injury

Long¹,

Gong²,

Eddy³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

Skp2 Regulates Subcellular Localization of PPARγ by MEK Signaling Pathways in Human Breast Cancer

Cited by 13 publications

References 31 publications

PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves

PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves

Cytoplasmic PPARγ is a marker of poor prognosis in patients with Cox-1 negative primary breast cancers

MEK1 regulates pulmonary macrophage inflammatory responses and resolution of acute lung injury

Contact Info

Product

Resources

About