The Dysregulation and Prognostic Analysis of STRIPAK Complex Across Cancers

Xie, Ruiling; Wen, Feng; Qin, Yong

doi:10.3389/fcell.2020.00625

Cited by 9 publications

(14 citation statements)

References 48 publications

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“…The dysregulated expression of metastasisassociated genes has been linked to the initiation, progression and prognosis of NSCLC [39] . In addition, STRIPAK complexes have shown to play an important role in cell growth, differentiation, proliferation and apoptosis of metabolism, immune regulation and tumor metastasis [11] . However, the current understanding of the function and possible mechanism of STRIP2 (STRIPAK major component) in NSCLC tumorigenesis is lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence has demonstrated that the STRIPAK genes were aberrantly expressed and served as a prognostic value in various cancer, such as STRN4 [40] , STRN3 [12] , STRIP1 [12,41] , STRIP2 [12,16] , MST4 [42] , MOB4 [42] , SLMAP [11] , PPP2R1A [11] , PDCD10 [11] and CTTNBP2NL [11] . In the present study, survival analysis using Kaplan-Meier Plotter online datasets revealed that patients with high STRIP2 expression had a poorer prognosis compared with those with low STRIP2 expression, suggesting that STRIP2 could be considered as a prognostic marker for NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

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STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Zhang

Chen

et al. 2022

Preprint

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Background: Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown. Methods: The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo. Results: Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitroand in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 mRNA stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes. Conclusions: Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Zhang

Chen

et al. 2022

Preprint

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“…Different combinations of these core proteins and accessory proteins results in the formation of different STRIPAK complexes. And it was reported that the STRIPAK complex plays many important roles in embryo development, cancer, diabetes, autism, and many other diseases, and regulates many important signaling pathways and cellular processes ( Hwang and Pallas, 2014 ; Wong et al, 2014 ; Zhang et al, 2014 ; Lant et al, 2015 ; Madsen et al, 2015 ; Sakuma et al, 2015 , 2016 ; Bazzi et al, 2017 ; Chursa et al, 2017 ; Huang et al, 2017 ; Pal et al, 2017 ; Zheng et al, 2017 ; Elramli et al, 2019 ; Kuck et al, 2019 ; Tang et al, 2019 ; Rodriguez-Cupello et al, 2020 ; Seo et al, 2020 ; Stein et al, 2020 ; Xie et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…The STRIPAK complex, an evolutionarily conserved supramolecular complex, is involved in many important physiological processes and diseases, including embryogenesis and development ( Lant et al, 2015 ; Sakuma et al, 2015 , 2016 ; Bazzi et al, 2017 ; Pal et al, 2017 ; Zheng et al, 2017 ), type 2 diabetes ( Chursa et al, 2017 ), and cancer progression ( Wong et al, 2014 ; Zhang et al, 2014 ; Madsen et al, 2015 ; Huang et al, 2017 ; Rodriguez-Cupello et al, 2020 ). The STRIPAK complex has several different formations depending on the combinations of different, mutually exclusive accessory proteins to the STRIPAK core components ( Hwang and Pallas, 2014 ; Kuck et al, 2019 ; Rodriguez-Cupello et al, 2020 ; Seo et al, 2020 ; Stein et al, 2020 ; Xie et al, 2020 ). Several important proteins combine to form the core STRIPAK components, including a striatin family member, the PP2A A/C heterodimer, Mob3, Strip1 or Strip2, and a GCKIII kinase bound via Ccm3 ( Goudreault et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Strip1 Expression in Mouse Cochlear Hair Cells

et al. 2021

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Striatin-interacting protein 1 (Strip1) is a core component of the striatin interacting phosphatase and kinase (STRIPAK) complex, which is involved in embryogenesis and development, circadian rhythms, type 2 diabetes, and cancer progression. However, the expression and role of Strip1 in the mammalian cochlea remains unclear. Here we studied the expression and function of Strip1 in the mouse cochlea by using Strip1 knockout mice. We first found that the mRNA and protein expression of Strip1 increases as mice age starting from postnatal day (P) 3 and reaches its highest expression level at P30 and that the expression of Strip1 can be detected by immunofluorescent staining starting from P14 only in cochlear HCs, and not in supporting cells (SCs). Next, we crossed Strip1 heterozygous knockout (Strip +/−) mice to obtain Strip1 homozygous knockout (Strip1−/−) mice for studying the role of Strip1 in cochlear HCs. However, no Strip1−/− mice were obtained and the ratio of Strip +/− to Strip1+/+ mice per litter was about 2:1, which suggested that homozygous Strip1 knockout is embryonic lethal. We measured hearing function and counted the HC number in P30 and P60 Strip +/− mice and found that they had normal hearing ability and HC numbers compared to Strip1+/+ mice. Our study suggested that Strip1 probably play important roles in HC development and maturation, which needs further study in the future.

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“…Other major components of STRIPAK complexes contain striatin-interacting protein 1 or 2 (STRIP1 or STRIP2, also named as family with sequence similarity 40 (FAM40) A or B), the MOB family member 4 protein (MOB4), the cerebral cavernous malformation 3 protein (CCM3), and the germinal center kinase III (GCKIII) family kinase (MST3, MST4, or STK25) [9,10]. Recently, STRIPAK complexes show many physiological and pathological functions, and dysregulation of STRIPAK components is participated in cancer [11]. Previous study has shown that STRIPAK components FAM40A, FAM40B, and STRN3 determine the model of cancer cell migration and metastasis through regulating the contractile cytoskeleton phenotype [12].…”

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confidence: 99%

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Zhang

Chen

et al. 2023

J Exp Clin Cancer Res

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Background Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown. Methods The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo. Results Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitro and in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes. Conclusions Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.

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The Dysregulation and Prognostic Analysis of STRIPAK Complex Across Cancers

Cited by 9 publications

References 48 publications

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Characterization of Strip1 Expression in Mouse Cochlear Hair Cells

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

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