RACK1 affects the progress of G2/M by regulating Aurora-A

Shen, Suqin; Feng, Huan; Le, Yichen; Ni, Jun; Liu, Yu; Wu, Jiaxue; Bai, Meirong

doi:10.1080/15384101.2019.1642065

Cited by 9 publications

(8 citation statements)

References 38 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated the critical roles of RACK1 in regulating the processes of cancer cell proliferation, adhesion, migration, invasion and metastasis (45)(46)(47)(48)(49). RACK1, ubiquitously expressed in a wide range of tissues, was initially identified as an anchoring protein for protein kinase C (55).…”

Section: Discussionmentioning

confidence: 99%

“…RACK1, which contains seven Trp-Asp 40 (WD40) repeats, is a scaffold protein with diverse functions that has been reported to interact with several receptors and regulate signaling pathways (45)(46)(47)(48)(49). To determine the functional significance of the association between CCDC102B and RACK1, we examined the expression level of RACK1 (Supplementary Figure 4B).…”

Section: Rack1 Decreases the Stability Of Ccdc102b Through The Lysoso...mentioning

confidence: 99%

See 1 more Smart Citation

Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway

Guo

Xiu

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundBreast cancer is one of the leading causes of cancer-related death among women, and the pathological status of axillary lymph nodes is an important predictor of prognosis. However, the mechanism involved in this early stage of metastasis remains largely unknown.MethodsMicroarray analysis was used to carry out differential genomics analyses between matched pairs of metastatic sentinel lymph node tissues and breast primary tumors. The CRISPR/Cas9 gene editing system was used for in vivo screening by transplanting a loss-of-function cell pool into immunocompromised mice. MAGeCK was used to analyze the screening results. Survival analysis was performed via the Kaplan–Meier method. Cell proliferation, wound healing, migration and invasion assays were performed to confirm the phenotype. A tail vein model and subcutaneous xenotransplanted tumor model were used for the in vivo study. The relationship between coiled-coil domain containing 102B (CCDC102B) and receptor for activated C kinase 1 (RACK1) was examined using coimmunoprecipitation, mass spectrometry, nuclear protein extraction and immunofluorescence assays. The primary biological functions and pathways related to CCDC102B were enriched by RNA sequencing.ResultsWe identified CCDC102B through screening and found that it was significantly upregulated in metastatic lesions in lymph nodes compared to matched primary tumors. Increased expression of CCDC102B promoted breast cancer metastasis in vitro and in vivo. Additionally, high expression of CCDC102B was correlated with poor clinical outcomes in breast cancer patients. We further identified that CCDC102B was stabilized by the loss of RACK1, a protein negatively correlated with breast cancer metastasis. Mechanistically, we found that RACK1 promoted CCDC102B lysosomal degradation by mediating chaperone-mediated autophagy (CMA). The aggressive behavior of CCDC102B in breast cancer cells could be reversed by the expression of RACK1. Moreover, CCDC102B was correlated with the significant enrichment of NF-κB pathway components. Overexpressing CCDC102B led to less interaction between RACK1 and IKKa. Thus, CCDC102B positively regulates the NF−κB pathway by interacting with RACK1.ConclusionTaken together, our findings uncover a novel role of CCDC102B in breast cancer metastasis. CCDC102B serves as a potential metastasis promoter by regulating the activation of the NF-κB pathway and can be degraded by RACK1 via CMA.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Rack1 Decreases the Stability Of Ccdc102b Through The Lysoso...mentioning

confidence: 99%

Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway

Guo

Xiu

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…However, how Aurora-A is activated is not fully understood. Some activators of Aurora-A are known, including the LIM-domain protein Ajuba ( Goyal et al, 1999 ; Hirota et al, 2003 ), the microtubule-associated protein TPX2 ( Eyers et al, 2003 ), p21-activated protein kinase 1 (Pak1) ( Zhao et al, 2005 ), thyroid hormone receptor-associated protein complex component/methyl-CpG binding endonuclease TRAP220/MED1 ( Udayakumar et al, 2006 ), EGFR ( Hung et al, 2008 ; Lai et al, 2010 ), ubiquitin-specific processing protease-7 (USP7) ( Giovinazzi et al, 2013 ), a classic tumor suppressor p53 ( Yang et al, 2018 ), heterogeneous nuclear ribonucleoprotein Q1 protein (HnRNP Q1) ( Lai et al, 2018 ), the receptor of activated C-kinase1 (RACK1) ( Shen et al, 2019 ), the NE proteins containing the LEM domain LEM4 ( Gao et al, 2018 ), and KIAA1529 ( Qiao et al, 2022 ). Most notably, EGF can increase Aurora-A gene expression through the nuclear EGFR/STAT5 signaling pathway and ultimately lead to chromosome instability and tumorigenesis ( Hung et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic acid suppresses apoptosis of high-grade serous ovarian cancer cells by inducing autophagy activity and promotes cell-cycle progression via EGFR-PI3K/Aurora-AThr288-geminin dual signaling pathways

et al. 2022

View full text Add to dashboard Cite

Lysophosphatidic acid (LPA) and geminin are overexpressed in ovarian cancer, and increasing evidence supports their contribution to ovarian tumor development. Here, we reveal that geminin depletion induces autophagy suppression and enhances reactive oxygen species (ROS) production and apoptosis of high-grade serous ovarian cancer (HGSOC) cells. Bioinformatics analysis and pharmacological inhibition studies confirm that LPA activates geminin expression in the early S phase in HGSOC cells via the LPAR1/3/MMPs/EGFR/PI3K/mTOR pathway. Furthermore, LPA phosphorylates Aurora-A kinase on Thr288 through EGFR transactivation, and this event potentiates additional geminin stabilization. In turn, overexpressed and stabilized geminin regulates DNA replication, cell-cycle progression, and cell proliferation of HGSOC cells. Our data provide potential targets for enhancing the clinical benefit of HGSOC precision medicine.

show abstract

“…The AURK family, consisting of AURKA, AURKB and AURKC in mammals, is a group of serine/threonine kinase enzymes. These mitotic kinases promote cell proliferation through involvement in the G2/M stage of the cell cycle [7,8]. Among these, AURKA and AURKB play important roles in the regulation of mitosis, whereas AURKC is speci cally expressed in mammalian testis.…”

Section: Introductionmentioning

confidence: 99%

The Expression and Prognosis for Aurora kinases in Human non-small cell lung cancer

Wang

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose Aurora kinases, as all known members of serine/threonine kinases genes family, have been found in various types of human cancer, playing their role as potent oncogenes. Increasing evidence showes that Aurora kinases are involved in lung cancer progression. However, the expression and clinical values of 3 types of Aurora kinases are still need to be further analyzed. Methods The expression and prognosis data of AURKs in patients with lung cancer were used to comprehensively analyze by multiple online databases including Cancer Genome Atlas (TCGA), Oncomine, gene expression profiling interactive analysis (GEPIA), Kaplan–Meier Plotter, cBioPortal, LinkedOmics.Immunohistochemistry (IHC) were also performed to explore AURKA and AURKB expression in LUAD. Results According to the results, the expression levels of AURKA and AURKB were higher in lung cancer tissues than in normal, whereas the AURKC expression was lower in lung cancer compared with normal. Both the AURKA and AURKB expression were positively correlated with advanced tumor stage in LUAD .Concurrently, AURKA was also significant positive correlated with advanced stage in LUSC. Survival analysis revealed that the high expression of AURKs were associated with low overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) of all of the patients with lung cancer especially in LUAD.AURKA and AURKB expression levels significantly correlated with immune cell infiltration and immune checkpoint genes in LUAD,suggested AURKA and AURKB were potential target for improving the efficacy of immunotherapy in LUAD patients. Conclusion In summary, this study implied that AURKA and AURKB are valuable markers for the prognosis of non-small cell lung cancer.

show abstract

RACK1 affects the progress of G2/M by regulating Aurora-A

Cited by 9 publications

References 38 publications

Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway

Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway

Lysophosphatidic acid suppresses apoptosis of high-grade serous ovarian cancer cells by inducing autophagy activity and promotes cell-cycle progression via EGFR-PI3K/Aurora-AThr288-geminin dual signaling pathways

The Expression and Prognosis for Aurora kinases in Human non-small cell lung cancer

Contact Info

Product

Resources

About