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PRR11 induces filopodia formation and promotes cell motility via recruiting arp2/3 complex in non-small cell lung cancer cells

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Genes & Diseases 2022年第1期9卷 230-244页

作者： Zhili Wei Ru Wang Xun Yin lian Zhang Yunlong Lei Ying Zhang Yi Li Jiaqian Wu Youquan Bu Guoxiang Jin Chundong Zhang Department of Biochemistry and Molecular Biology Chongqing Medical UniversityChongqing 400016PR China Molecular Medicine and Cancer Research Center Chongqing Medical UniversityChongqing 400016PR China Guangdong Provincial People’s Hospital Guangdong Academy of Medical SciencesGuangzhouGuangdong 510080PR China

Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (arp2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the arp2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling. In this study, we further demonstrate that PRR11 involves in filopodia formation, focal adhesion turnover and cell motility through arp2/3 complex. Cell phenotype assays revealed that the silencing of PRR11 increased cellular size and inhibited cell motility in NSCLC cells. Mechanistically, PRR11 recruited and co-localized with arp2 at the membrane protrusion to promote filopodia formation but not lamellipodia formation. Notably, PRR11 mutant deletion of the proline-rich region 2 (amino acid residues 185–200) abrogated the effect of filopodia formation. In addition, PRR11-depletion inhibited filopodial actin filaments assembly and increased the level of active integrin β1 in the cell surface, whereas reduced the phosphorylation level of focal adhesion kinase (FAKY397) to repress focal adhesion turnover and cell motility in NSCLC cells. Taken together, our findings indicate that PRR11 has critical roles in controlling filopodia formation, focal adhesion turnover and cell motility by recruiting arp2/3 complex, thus dysregualted expression of PRR11 potentially facilitates tumor metastasis in NSCLC cells.

关键词： arp2/3 complex Cell motility FAK Filopodia Focal adhesion Integrin NSCLC cells PRR11

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The role of viral protein Ac34 in nuclear relocation of subunits of the actin-related protein 2/3 complex

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Virologica Sinica 2016年第6期31卷 480-489页

作者： Jingfang Mu Yongli Zhang Yangyang Hu Xue Hu Yuan Zhou Xinwen Chen Yun Wang State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China University of Chinese Academy of Sciences Beijing 100049 China

The actin nucleator actin-related protein complex(arp2/3) is composed of seven subunits: arp2,arp3, p40/arpC1(P40), p34/arpC2(P34), p21/arpC3(P21), p20/arpC4(P20), and p16/arpC5(P16). arp2/3 plays crucial roles in a variety of cellular activities through regulation of actin polymerization. Autographa californica multiple nucleopolyhedrovirus(Ac MNPV), one of the beststudied alphabaculoviruses, induces arp2/3 nuclear relocation and mediates nuclear actin polymerization to assist in virus replication. We have demonstrated that Ac34, a viral late-gene product, induces translocation of the P40 subunit of arp2/3 to the nucleus during Ac MNPV infection. However, it remains unknown whether Ac34 could relocate other arp2/3 subunits to the nucleus. In this study, the effects of the viral protein Ac34 on the distribution of these subunits were studied by an immunofluorescence assay. arp2, P34, P21, and P20 cloned from Spodoptera frugiperda(Sf9) cells showed mainly cytoplasmic localization and were relocated to the nucleus in the presence of Ac34. In addition, arp3 was localized in the cytoplasm in both the presence and absence of Ac34, and P16 showed whole-cell localization. In contrast to Sf9 cells, all subunits of mammalian arp2/3 showed no nuclear relocation in the presence of Ac34. Co-immunoprecipitation analysis of the interaction between Ac34 and arp2/3 subunits revealed that Ac34 bound to P40,P34, and P20 of Sf9 cells. However, none of the subunits of mammalian arp2/3 interacted with Ac34, indicating that protein-protein interaction is essential for Ac34 to relocate arp2/3 subunits to the nucleus.

关键词： Autographa californica multiple nucleopolyhedrovirus(AcMNPV) Ac34 arp2/3 complex nuclear relocation

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Clinicopathological and prognostic significance of aberrant arpin expression in gastric cancer

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World Journal of Gastroenterology 2017年第8期23卷 1450-1457页

作者： Tao Li Hong-Mei Zheng Nai-Mei Deng Ying-Jian Jiang Jiang Wang Dian-Liang Zhang Center of Colon and Rectum Qingdao Municipal HospitalQingdao University Infection Department Qingdao Municipal Hospital

AIM To detect the expression of arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the arpin and arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the arpin protein in 43 normal gastric tissues was also determined using IHC. RESULTS Expression of the arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P 2) test of the 176 GC samples used for IHC showed that decreased arpin expression was associated with advanced TNM stage (P 2% vs 35.56%, P arpin and the presence of the arp2/3 complex in GC tissues (chi(2) = 30.535, P arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low arpin expression levels (median DFS 19 mo) was higher than that in the high-arpin-expression group (median DFS 34 mo, P = 0.022). CONCLUSION Low arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. arpin may be regarded as a potential prognostic indicator in GC.

关键词： clinicopathological characteristics Gastric cancer arpin arp2/3 complex Prognosis

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