CD147 regulates cancer migration <i>via</i> direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling

Cui, Hong‐Yong; Wang, Shijie; Miao, Jiyu; Fu, Zhi-Guang; Fěng, Fang; Wu, Jiao; Yang, Xiang-Min; Chen, Zhi‐Nan; Jiang, Jian‐Li

doi:10.18632/oncotarget.6723

Cited by 32 publications

(29 citation statements)

References 52 publications

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“…Recently, the Rac1/WAVE2/Arp2/3 signaling pathway was reported to promote cell migration and invasion of glioma cells and liver cancer cells . The WAVE2/Annexin A2/DOCK3/β‐catenin signaling pathway promotes the invasiveness and metastasis of liver cancer cells . These findings indicated that WAVE2‐associated signaling pathways play important roles in cell invasion and metastasis in various types of cancer cells.…”

Section: Discussionmentioning

confidence: 92%

WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

et al. 2018

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WAVE2 is a member of the WASP/WAVE family of actin cytoskeletal regulatory proteins; unfortunately, little is known about its function in pancreatic cancers. In this study, we report the role of WAVE2 in the motility and invasiveness of pancreatic cancer cells. High WAVE2 expression in human pancreatic cancer tissues was correlated with overall survival. WAVE2 accumulated in the cell protrusions of pancreatic cancer cell lines. Downregulation of WAVE2 by small interfering RNA decreased the cell protrusions and inhibited the motility and invasiveness of pancreatic cancer cells. WAVE2 promoted pancreatic cancer cell motility and invasion by forming a complex with the actin cytoskeletal protein alpha‐actinin 4 (ACTN4). Downregulation of ACTN4 by small interfering RNA also inhibited the motility and invasiveness of the cells through a decrease in cell protrusions. Further investigation showed that WAVE2/ACTN4 signaling selectively stimulated p27 phosphorylation and thereby increased the motility and invasiveness of the cells. These results suggest that WAVE2 and ACTN4 stimulate p27 phosphorylation and provide evidence that WAVE2 promotes the motility and invasiveness of pancreatic cancer cells.

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Section: Discussionmentioning

confidence: 92%

WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

et al. 2018

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“…Emerging evidence identified interaction of ANX A2 with Semaphorin 3D (sema3D) and CD147. Moreover, these interactions initiates DOCK3‐β‐catenin‐WAVE2 signaling leading to cell migration, invasion and metastasis . However, involvement of ANX A2 in these signaling pathways in vivo is yet to be established.…”

Section: Introductionmentioning

confidence: 99%

Annexin A2 (ANX A2): An emerging biomarker and potential therapeutic target for aggressive cancers

Sharma

2018

Intl Journal of Cancer

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ANX A2 is an important member of annexin family of proteins expressed on surface of endothelial cells (ECs), macrophages, mononuclear cells and various types of cancer cells. It exhibits high affinity binding for calcium (Ca ) and phospholipids. ANX A2 plays an important role in many biological processes such as endocytosis, exocytosis, autophagy, cell-cell communications and biochemical activation of plasminogen. On the cell surface ANX A2 organizes the assembly of plasminogen (PLG) and tissue plasminogen activator (tPA) for efficient conversion of PLG to plasmin, a serine protease. Proteolytic activity of plasmin is required for activation of inactive pro-metalloproteases (pro-MMPs) and latent growth factors for their biological actions. These activation steps are critical for degradation of extracellular matrix (ECM) and basement proteins (BM) for cancer cell invasion and metastasis. Increased expression of ANX A2 protein/gene has been correlated with invasion and metastasis in a variety of human cancers. Moreover, clinical studies have positively correlated ANX A2 protein expression with aggressive cancers and with resistance to anticancer drugs, shorter disease-free survival (DFS), and worse overall survival (OS). The mechanism(s) by which ANX A2 regulates cancer invasion and metastasis are beginning to emerge. Investigators used various technologies to target ANX A2 in preclinical model of human cancers and demonstrated exciting results. In this review article, we analyzed existing literature concurrent with our own findings and provided a critical overview of ANX A2-dependent mechanism(s) of cancer invasion and metastasis.

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“…HFF-1 cells were obtained from American Type Culture Collection (ATCC, USA). A Huh-7 CD147-KO (Huh-7 CD147 −/− ) cell line was generated using a CRISPR/Cas9 system as previously reported [24]. All cells were cultured at 37℃, 5% CO 2 , in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS).…”

Section: Cell Linesmentioning

confidence: 99%

CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma

Wang

Chen

Wei

et al. 2020

Preprint

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Background Mounting evidence suggests that solid tumors display the features of collective invasion, however, the molecular mechanisms are far from clear. This study aims to verify the role and the underlying mechanisms of CD147 in collective invasion in hepatocellular carcinoma. Methods Immunostaining was used to analyze human hepatocellular carcinoma specimens and three-dimensional cultures. Three-dimensional invasion model was established to mimic in vivo invasion. RNA-sequencing was used to identify downstream effectors. Results Human hepatocellular carcinoma undergone collective invasion and CD147 was observed to be upregulated at the invasive front of tumor cell groups. CD147 was demonstrated to promote collective invasion using the modified three-dimensional invasion model, which recapitulated the main features of collective invasion. Through transcriptome analysis and enzyme activity assay, we found that CD147 enhanced cathepsin B expression and activation. Upregulated cathepsin B in hepatocellular carcinoma cells facilitated migration and invasion, which mediated CD147-induced invasive phenotype in hepatocellular carcinoma. In terms of mechanism, we found that CD147 promoted cathepsin B transcription by activating β-catenin signaling as a result of reduced GSK-3β expression. Furthermore, we found that elevated expression of CD147 as well as cathepsin B were correlated with poor prognosis in patients with hepatocellular carcinoma. Conclusions CD147 promotes hepatocellular carcinoma cells collective invasion via upregulating cathepsin B expression and targeting CD147 would be valuable for the development of novel therapeutic modalities against invasion and metastasis of cancer.

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CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling

Cited by 32 publications

References 52 publications

WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

Annexin A2 (ANX A2): An emerging biomarker and potential therapeutic target for aggressive cancers

CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma

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