PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis

Yao, Xing; Li, Yang; Hu, Bingtao; Han, Fuyi; Zhao, Xin; Zhang, Hongyan; Li, Yanshu; Li, Danni; Li, Jiabin; Jin, Feng; Li, Feng

doi:10.7150/ijbs.58102

Cited by 12 publications

(9 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(18) In breast cancer, PAK5 phosphorylates apoptosis-inducing factor (AIF) at Thr281 site to prevent the formation of AIF/importin α3 complex, leading to decrease AIF nuclear translocation and inhibiting cancer cells caspase-independent apoptosis. (3) Previous studies have con rmed that activation of PAK5 signaling pathway conduces activation or inhibition of several transcription factors, including EGR1. (22) RAF1, (23) etc., which subsequently enhance or suppress multiplex biological activities.…”

Section: Resultsmentioning

confidence: 98%

“…There are six members in PAK family including group (PAK1-3) and group (PAK4-6) based on the structural similarities, they are known to be important signaling effectors which interact with a wide array of intracellular proteins to mediate cell proliferation and motility, as well as cell transformation and tumor progression. (2) Overexpressed PAK5 has been implicated in cancer phenotype in several malignancies including breast, lung, kidney, liver, colon, and ovarian cancers by interacting with AIF, (3) SOX2, (4) SMUC, (5) β-catenin, (6) Integrin β1, (7) and PI3K/AKT. (8) However, the underlying role of PAK5 and its substrate in leukemic cells still waits to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PAK5 is a potential target in myelodysplastic syndrome through interacting with LMO2 and GATA1

Pan

Liu²,

Ying

et al. 2022

Preprint

View full text Add to dashboard Cite

Myelodysplastic syndrome (MDS) is a neoplastic heterogeneous and pre-leukemic disease with poor clinical outcome due to the failure of current chemotherapeutic strategies to target leukemic stem cells. Recently, we find that p21-activated kinase 5 (PAK5) overexpresses in MDS patients and leukemia cell lines. The clinical and prognostic value of PAK5 in MDS is unclear although it has anti-apoptosis ability and can promote cell survival and mobility in solid tumors. In this study, we find that LMO2 is co-expressed with PAK5 in the aberrant cells from MDS, and mitochondria-localized PAK5 can translocate into cell nucleus upon fetal bovine serum stimulation to interact with LMO2 and GATA1, which are important transcription regulators in hematological malignancies. Interestingly, without LMO2, PAK5 fails to bind GATA1 and facilitate GATA1 Ser161 site phosphorylation, indicating that PAK5 may be a key kinase in LMO2-associated hematopoietic diseases. Moreover, we find that PAK5 protein level in MDS is significantly higher than leukemia, and the data of 2095 leukemia samples from ‘BloodSpot’ database shows that PAK5 mRNA level in MDS is also increased obviously. Taken together, our findings suggest that PAK5-targeted strategies in clinical therapy have a potential value on MDS intervention.

show abstract

Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

PAK5 is a potential target in myelodysplastic syndrome through interacting with LMO2 and GATA1

Pan

Liu²,

Ying

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…AIF-1 + CSF1R + MSCs, induced by TNF-α, generate an inflammatory microenvironment and promote hepatocarcinogenesis [41]. Furthermore, the PAK5-AIF signaling pathway may play an essential role in mammary tumorigenesis, providing a new therapeutic target for breast cancer treatment [42].…”

Section: Discussionmentioning

confidence: 99%

Allograft inflammatory factor 1 is a potential diagnostic, immunological, and prognostic biomarker in pan-cancer

Liu

Zhang

et al. 2023

Aging

View full text Add to dashboard Cite

Background: Allograft Inflammatory Factor 1 (AIF-1) is a member of the allograft inflammatory factor gene family and plays an essential role in the occurrence and development of malignant tumors. However, little is known about the expression pattern, predictive value, and biological function of AIF-1 across cancers. Materials and Methods: We first analyzed AIF-1 expression across cancers based on data from public databases. Univariate Cox regression and Kaplan-Meier analyses were used to explore the predictive value of AIF-1 expression in various cancers. Moreover, gene set enrichment analysis (GSEA) was applied to determine the cancer hallmarks associated with AIF-1 expression. Spearman correlation analysis was performed to investigate the association between AIF-1 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, and DNA methyltransferases. Results: AIF-1 expression was upregulated in most cancer types and exhibited prognosis-predictive ability. AIF-1 expression was positively correlated with immune infiltrating cells and immune checkpoint-related genes in most cancers. Additionally, the promoter methylation level of AIF-1 was different in distinct tumors. High methylation levels of AIF-1 were associated with a worse prognosis in UCEC and melanoma, whereas they were associated with a better prognosis in GBM, KIRC, OV, and UVM. Finally, we found that AIF-1 was significantly highly expressed in KIRC tissues. Functionally, silencing AIF-1 dramatically decreased proliferation, migration, and invasion abilities. Conclusion: Our results reveal that AIF-1 acts as a robust tumor biomarker and is closely correlated with tumor immune infiltration. Furthermore, AIF-1 may function as an oncogene and promote tumor progression in KIRC.

show abstract

“…Moreover, the overexpression of mature AIF proteins can be further amplified by activating caspase-7 and affecting the cleavage of eIF3g ( 37 ). Furthermore, some other molecules, such as PARP1 ( 41 ), Harlequin ( 42 ), and PAK5 ( 43 ), have also been identified to influence AIF expression directly or indirectly.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-inducing factor: a mitochondrial protein associated with metabolic diseases—a narrative review

Zong¹,

Zhou²

2023

Cardiovasc Diagn Ther

View full text Add to dashboard Cite

Background and Objective Apoptosis-inducing factor (AIF), a flavin protein in mitochondria, is originally found to induce apoptosis under the stimulation of pro-apoptotic factors. As a mitochondrial flavin adenine dinucleotide-dependent oxidoreductase, AIF is involved in the regulation of mammalian cell metabolism by regulating respiratory enzyme activity, antioxidant stress, promoting mitochondrial autophagy and glucose uptake, etc. Herein, we focused on the research progress regarding the molecular mechanism of AIF in metabolic mediation and the recent research on AIF in metabolic diseases, as well as the AIF-mediated apoptotic process. Methods Articles for this paper were obtained by reviewing the literature related to the role of AIF in metabolic diseases on PubMed. The search terms included the following: “apoptosis”, “metabolism” or “metabolic diseases” plus “apoptosis-inducing factor”. The titles, abstracts, and full texts of relevant English-language publications published from October 1996 to June 2022 were manually screened to clarify the role of AIF in metabolic diseases. Key Content and Findings We found that AIF played an important role in a variety of metabolically-related diseases, such as diabetes, obesity, metabolic syndrome, and tumor metabolism, by mediating apoptosis. Conclusions We summarized the important role of AIF in a variety of metabolic diseases, which might help to further expand the understanding of AIF and to develop AIF-related therapeutic targets.

show abstract

PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis

Cited by 12 publications

References 37 publications

PAK5 is a potential target in myelodysplastic syndrome through interacting with LMO2 and GATA1

PAK5 is a potential target in myelodysplastic syndrome through interacting with LMO2 and GATA1

Allograft inflammatory factor 1 is a potential diagnostic, immunological, and prognostic biomarker in pan-cancer

Apoptosis-inducing factor: a mitochondrial protein associated with metabolic diseases—a narrative review

Contact Info

Product

Resources

About