SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer

An, Juan; Yang, Lang; Pan, Yuanming; He, Yuqi; Xie, Hui; Tao, Yurong; Li, Wei; Yan, Yupeng; Chen, Siai; Liu, Ya; Ma, Xiaoming; An, Ling; Ji, Dongde; Su, Zhanhai; Sheng, Jian-qiu

doi:10.1089/dna.2021.0531

Cited by 7 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Twenty genes, including ENKUR, WD repeat domain 62 (WDR62) , SEPTIN11 , SUV39H1 histone lysine methyltransferase (SUV39H1) , SH3 and cysteine rich domain 3 (STAC3) , Dishevelled segment polarity protein 3 (DVL3) , Makorin ring finger protein 3 (MKRN3) , MDF1 , PNMA family member 2 (PNMA2) , Tyrosine 3‐monooxygenase/tryptophan 5‐monooxygenase activation protein epsilon (YWHAE) , Kallikrein related peptidase 11 (KLK11) , Exportin 1 (XPO1) , Centrosomal protein 164 (CEP164) , Cation channel sperm associated auxiliary subunit beta (CATSPERB) , Exocyst complex component 3 (EXOC3) , C12orf65 , WDR91 , TP53 target 3 (TP53TG3) , Hypoxia upregulated 1 (HYOU1) , and SPAG5 , were predicted to interact with ENKD1 (Figure 6l). It has been reported that ENKUR and SPAG5 are involved in the regulation of several types of cancer (An et al, 2022; Hou et al, 2022; Y. F. Yang et al, 2018; Yuan et al, 2014). These findings suggest that ENKD1 may participate in the regulation of DLBCL through interactions with SPAG5 and ENKUR .…”

Section: Resultsmentioning

confidence: 99%

“…Sperm‐associated antigen 5 (SPAG5), an important mitosis and cell cycle checkpoint regulator, is attracting attention as a novel oncogene in various cancers. For example, SPAG5 promoted gastric cancer cell growth by regulating the PI3K/AKT signaling pathway and may be a promising therapy target in gastric cancer (An et al, 2022). The carcinogenic function of SPAG5 may be mediated by miRNAs, with miR‐539 inhibiting prostate cancer progression by directly targeting SPAG5 (H. Zhang et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…We also analyzed genes that interact with ENKD1 using the Centrosomal protein 164 (CEP164), Cation channel sperm associated auxiliary subunit beta (CATSPERB), Exocyst complex component 3 (EXOC3), C12orf65, WDR91, TP53 target 3 (TP53TG3), Hypoxia upregulated 1 (HYOU1), and SPAG5, were predicted to interact with ENKD1 (Figure 6l). It has been reported that ENKUR and SPAG5 are involved in the regulation of several types of cancer (An et al, 2022;Hou et al, 2022;Y. F. Yang et al, 2018;Yuan et al, 2014).…”

Section: Enkd1 Expression Correlates With the Expression Of Various R...mentioning

confidence: 99%

See 2 more Smart Citations

Upregulation of ENKD1 disrupts cellular homeostasis to promote lymphoma development

Song

Hao

et al. 2023

Journal Cellular Physiology

View full text Add to dashboard Cite

Diffuse large B cell lymphoma (DLBCL) is a common and aggressive form of B cell lymphoma. Approximately 40% of DLBCL patients are incurable despite modern therapeutic approaches. To explore the molecular mechanisms driving the growth and progression of DLBCL, we analyzed genes with differential expression in DLBCL using the Gene Expression Profiling Interactive Analysis database. Enkurin domain‐containing protein 1 (ENKD1), a centrosomal protein‐encoding gene, was found to be highly expressed in DLBCL samples compared with normal samples. The phylogenetic analysis revealed that ENKD1 is evolutionarily conserved. Depletion of ENKD1 in cultured DLBCL cells induced apoptosis, suppressed cell proliferation, and blocked cell cycle progression in the G2/M phase. Moreover, ENKD1 expression positively correlates with the expression levels of a number of cellular homeostatic regulators, including Sperm‐associated antigen 5, a gene encoding an important mitotic regulator. These findings thus demonstrate a critical function for ENKD1 in regulating the cellular homeostasis and suggest a potential value of targeting ENKD1 for the treatment of DLBCL.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Enkd1 Expression Correlates With the Expression Of Various R...mentioning

confidence: 99%

See 1 more Smart Citation

Upregulation of ENKD1 disrupts cellular homeostasis to promote lymphoma development

Song

Hao

et al. 2023

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…In addition, we speculate that some mitotic regulatory factors may be involved in this process ( Figure 9 ). During mitosis, PLK1 interacts and phosphorylates the N-terminus of SPAG5 (also known as astrin) [ 38 , 39 , 40 ], which has been reported to upregulate the PI3K/AKT pathway in cancer cells in vitro [ 41 , 42 , 43 , 44 ] through the centrosome protein CEP55 [ 45 ]. In Xenopus , Gwl (MASTL in humans) also interacts with and is phosphorylated by PLK1 during the cell cycle [ 46 ].…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells

Zhao,

Liu,

Tan

et al. 2024

Biology

View full text Add to dashboard Cite

E. sinensis is an animal model for studying the reproduction and development of crustaceans. In this study, we knocked down the Es-Kif2a gene by injecting dsRNA into E. sinensis and inhibited Es-Plk1 gene expression by injecting PLK1 inhibitor BI6727 into E. sinensis. Then, the cell proliferation level, apoptosis level, and PI3K/AKT signaling expression level were detected. Our results showed that the proliferation level of spermatogenic cells decreased, while the apoptosis level increased after Es-Kif2a knockdown or Es-Plk1 inhibition. In order to verify whether these changes are caused by regulating the PI3K/AKT pathway, we detected the expression of PI3K and AKT proteins after Es-Kif2a knockdown or Es-Plk1 inhibition. Western Blot showed that in both the Es-Kif2a knockdown group and the Es-Plk1 inhibition group, the expression of PI3K and AKT proteins decreased. In addition, immunofluorescence showed that Es-KIF2A and Es-PLK1 proteins were co-localized during E. sinensis spermatogenesis. To further explore the upstream and downstream relationship between Es-KIF2A and Es-PLK1, we detected the expression level of Es-PLK1 after Es-Kif2a knockdown as well as the expression level of Es-KIF2A after Es-Plk1 inhibition. Western Blot showed that the expression of Es-PLK1 decreased after Es-Kif2a knockdown, while there was no significant change of Es-KIF2A after Es-Plk1 inhibition, indicating that Es-PLK1 may be a downstream factor of Es-KIF2A. Taken together, these results suggest that Es-KIF2A upregulates the PI3K/AKT signaling pathway through Es-PLK1 during the spermatogenesis of E. sinensis, thereby affecting the proliferation and apoptosis levels of spermatogenic cells.

show abstract

“…PI3K/Akt/mTOR is a key signaling pathway that regulates autophagy, and then affects the development of cardiovascular diseases [ 31 , 32 ]. Previous studies have reported that SPAG5 triggers PI3K/AKT signaling pathway to exert oncogenic activities in various cancers, such as hepatocellular carcinoma, and gastric cancer [ 20 , 33 ]. Consistently, PI3K/Akt/mTOR signaling pathway was inactivated by SPAG5 knockdown in ox-LDL-treated HUVECs.…”

Section: Discussionmentioning

confidence: 99%

SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE−/− mice

Guo,

Yuan,

Zhu

et al. 2024

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical autophagy pathway, PI3K/Akt/mTOR signaling pathway. This work attempted to investigate whether SPAG5 can affect AS development by regulating autophagy. Methods Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low density lipoprotein (ox-LDL) to induce cell damage. ApoE−/− mice were fed a Western diet to establish an AS mouse model. Haematoxylin and eosin (H&E) staining and Oil Red O staining evaluated the pathological changes and in lipid deposition in aortic tissues. CCK-8 and flow cytometry detected cell proliferation and apoptosis. Immunohistochemistry, Enzyme linked immunosorbent assay, qRT-PCR and western blotting assessed the levels of mRNA and proteins. Results Ox-LDL treatment elevated SPAG5 expression and the expression of autophagy-related proteins, LC3-I, LC3-II, Beclin-1, and p62, in HUVECs. GFP-LC3 dots were increased in ox-LDL-treated HUVECs and LPS-treated HUVECs. SPAG5 knockdown reversed both ox-LDL and LPS treatment-mediated inhibition of cell proliferation and promotion of apoptosis in HUVECs. SPAG5 silencing further elevated autophagy and repressed the expression of PI3K, p-Akt/Akt, and p-mTOR/mTOR in ox-LDL-treated HUVECs. 3-MA (autophagy inhibitor) treatment reversed SPAG5 silencing-mediated increase of cell proliferation and decrease of apoptosis in ox-LDL-treated HUVECs. In vivo, SPAG5 knockdown reduced atherosclerotic plaques in AS mice through activating autophagy and inhibiting PI3K/Akt/mTOR signaling pathway. Conclusion This work demonstrated that SPAG5 knockdown alleviated AS development through activating autophagy. Thus, SPAG5 may be a potential target for AS therapy.

show abstract

SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer

Cited by 7 publications

References 26 publications

Upregulation of ENKD1 disrupts cellular homeostasis to promote lymphoma development

Upregulation of ENKD1 disrupts cellular homeostasis to promote lymphoma development

KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells

SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE−/− mice

Contact Info

Product

Resources

About