Role of ARPC2 in Human Gastric Cancer

Zhang, Jun; Liu, Yi; Yu, Changjun; Dai, Fang; Xiong, Jessie; Li, Hong-Jun; Wu, Zhengsheng; Ding, Rui; Wang, Hong

doi:10.1155/2017/5432818

Cited by 22 publications

(22 citation statements)

References 44 publications

(40 reference statements)

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“…As reported previously, the silencing of the ARP2/3 complex decreased the migration of pancreatic cancer cells (33). Zhang et al reported that ARPC2 promoted the proliferation and invasion of the human gastric cancer cell line, MKN-28; ARPC2 exhibited a higher expression in gastric cancer tissues than in normal gastric tissues; ARPC2 was significantly associated with a large tumor size, lymph node invasion, and a high tumor stage of gastric cancer patients; ARPC2-positive patients exhibited lower RFS and OS rates compared with ARPC2-negative patients (34). These data all support our present results.…”

Section: Discussionsupporting

confidence: 91%

RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression

et al. 2019

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Breast cancer is one of the most common types of cancers which results in a high mortality rate for patients worldwide. In this study, we performed systematical experiments including tissue analysis (immunohistochemistry etc.) and cell functional experiments (cell counting assay, MTT assay, cell colony formation, cell migration assay, cell invasion assay etc.). We demonstrated that the expression level of RNA binding motif protein 3 (RBM3) was higher in human breast cancer tissues compared with adjacent non-tumor tissues. A high level of RBM3 was associated with worse post-operative relapse-free survival (RFS) and overall survival (OS) rates in patients with breast cancer. Among the patients with breast cancer, the expression of RBM3 was associated with patient lymph node metastasis and a high tumor grade. The knockdown of RBM3 markedly decreased the proliferation and metastasis of human breast cancer cells. In downstream pathway analysis, actin related protein 2/3 complex subunit 2 (ARPC2) was determined to be positively regulated by RBM3 through a post-transcriptional 3'UTR-binding manner. ARPC2 also played an oncogenic role and mediated the promoting role of RBM3 in the proliferation and metastasis of human breast cancer cells. Thus, on the whole, the findings of this study demonstrate that RBM3 acts as an oncogene in human breast cancer cells and that the functional depletion of RBM3 may be considered as a potential method for breast cancer therapy.

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Section: Discussionsupporting

confidence: 91%

RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression

et al. 2019

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“…ARPC2 is one of the subunits of the Arp2/3 complex and is required for maintaining the structural integrity of the entire complex. ARPC2 expression is associated with metastasis and poor prognosis of patients with melanoma or gastric tumors . Recently, we reported that ARPC2 inhibitor (benproperine, Benp) suppressed the migration and invasion of cancer cells and tumor metastasis in animal models .…”

Section: Introductionmentioning

confidence: 99%

Pimozide suppresses cancer cell migration and tumor metastasis through binding to ARPC2, a subunit of the Arp2/3 complex

et al. 2019

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ARPC2 is a subunit of the Arp2/3 complex, which is essential for lamellipodia, invadopodia and filopodia, and ARPC2 has been identified as a migrastatic target molecule. To identify ARPC2 inhibitors, we generated an ARPC2 knockout DLD‐1 human colon cancer cell line using the clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9) system and explored gene signature‐based strategies, such as a connectivity map (CMap) using the gene expression profiling data of ARPC2 knockout and knockdown cells. From the CMap‐based drug discovery strategy, we identified pimozide (a clinically used antipsychotic drug) as a migrastatic drug and ARPC2 inhibitor. Pimozide inhibited the migration and invasion of various cancer cells. Through drug affinity responsive target stability (DARTS) analysis and cellular thermal shift assay (CETSA), it was confirmed that pimozide directly binds to ARPC2. Pimozide increased the lag phase of Arp2/3 complex‐dependent actin polymerization and inhibited the vinculin‐mediated recruitment of ARPC2 to focal adhesions in cancer cells. To validate the likely binding of pimozide to ARPC2, mutant cells, including ARPC2F225A, ARPC2F247A and ARPC2Y250F cells, were prepared using ARPC2 knockout cells prepared by gene‐editing technology. Pimozide strongly inhibited the migration of mutant cells because the mutated ARPC2 likely has a larger binding pocket than the wild‐type ARPC2. Therefore, pimozide is a potential ARPC2 inhibitor, and ARPC2 is a new molecular target. Taken together, the results of the present study provide new insights into the molecular mechanism and target that are responsible for the antitumor and antimetastatic activity of pimozide.

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“…Among these subunits, ARPC2 (subunit 2, 34 kDa) has a fundamental role in the nucleation of actin filaments (AFs) and participates in the polarization of the Golgi apparatus (11). Al Ghouleh et al demonstrated that ARPC2 participates in smooth muscle cell migration (12), Zhang et al also reported that ARPC2 may be involved in human gastric cancer cell proliferation or migration (13). Thus ARPC2 is critical to cell migration and invasion (14).…”

Section: Introductionmentioning

confidence: 99%

ARPC2 promotes breast cancer proliferation and metastasis

Cheng

Wei

et al. 2019

Oncol Rep

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Actin-related protein 2/3 complex (ARPC2) is an actin-binding component involved in the regulation of actin polymerization. It mediates the formation of branched actin networks and contacts the mother actin filament. Migration and invasion are key processes which enable tumor cells to infiltrate blood vessels or lymphatic vessels, and the actin pathway plays a very important role. Given that ARPC2 is critical to this progression, the present study focused on ARPC2 activity in breast cancer (BrCa) cell invasion and migration. Limited data are available on the expression and role of ARPC2 proteins in breast carcinomas. We screened the Oncomine database for messenger RNAs (mRNAs) that are upregulated in BrCa and found that ARPC2 was one of the most consistently involved mRNAs in BrCa. The analysis of immunohistochemical data revealed that ARPC2 expression was higher in breast cancerous tissues than in adjacent non-cancerous tissues. In addition, ARPC2 was highly associated with the tumor stage, nodal metastasis, and overall survival of patients with BrCa. We performed siRNA-ARPC2 transfection to investigate the effect of ARPC2 on the proliferation, migration, invasion and arrest of BrCa cells. It was revealed that ectopic ARPC2 expression significantly upregulated N-cadherin, vimentin, ZEB1, MMP-9 and MMP-3 expression and also activated the TGF-β pathway to contribute to epithelial-mesenchymal transition (EMT). These results collectively indicated that ARPC2 promoted the tumorigenesis of breast carcinoma and the initiation of EMT. Therefore, ARPC2 was revealed to be a potential therapeutic target in patients with BrCa.

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Role of ARPC2 in Human Gastric Cancer

Cited by 22 publications

References 44 publications

RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression

RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression

Pimozide suppresses cancer cell migration and tumor metastasis through binding to ARPC2, a subunit of the Arp2/3 complex

ARPC2 promotes breast cancer proliferation and metastasis

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