Zyxin as a potential cancer prognostic marker promotes the proliferation and metastasis of colorectal cancer cells

Zhong, Chenhan; Yu, Jingping; Li, Dan; Jiang, Kai; Tang, Yang; Yang, Mengyuan; Shen, Hong; Fang, Xuefeng; Ding, Kefeng; Zheng, Shu; Yuan, Ying

doi:10.1002/jcp.28236

Cited by 18 publications

(17 citation statements)

References 62 publications

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“…6) [42][43][44][45][46][47][48] . This is in agreement with observations that zyxin influences cell migration, adhesion and proliferation as well as its potential involvement in cancer progression [49][50][51][52][53] . Zyxin's role in regulating cell survival is controversial [27][28][29][30] , but nuclear activities have generally been related to antiapoptotic effects 15,16 .…”

Section: Discussionsupporting

confidence: 92%

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

2020

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Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrates (TAILS) we had characterized proteolytic signatures in a porcine wound healing model and identified two neoN termini derived from proteolytic cleavage of the focal adhesion protein and mechanotransducer zyxin. Here, we assign these proteolytic events to the activity of either caspase-1 or serine protease HtrA1 and analyze the biological relevance of the resultant zyxin truncations. By cellular expression of full-length and truncated zyxin proteins, we demonstrate nuclear translocation of a C-terminal zyxin fragment that could also be generated in vitro by HtrA1 cleavage and provide evidence for its anti-apoptotic activities, potentially by regulating the expression of modulators of cell proliferation, protein synthesis and genome stability. Targeted degradomics correlated endogenous generation of the same zyxin fragment with increased cell density in human primary dermal fibroblasts. Hence, this newly identified HtrA1-zyxin protease signaling axis might present a novel mechanism to transiently enhance cell survival in environments of increased cell density like in wound granulation tissue.

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Section: Discussionsupporting

confidence: 92%

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

2020

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“…In vitro experiments demonstrated that ZYX silencing in HCT116 colorectal cancer cell line caused decreased cell migration and invasion (58).…”

Section: Melanoma Elevated Levels Of Zyx Were Observed In Melanoma Cmentioning

confidence: 99%

“…Zhong et al showed that ZYX expression was significantly higher in colorectal cancer lesions in comparison to normal tissues (58). The patients with tumours characterised by high ZYX expression had a shorter recurrence-free survival (58).…”

Section: Melanoma Elevated Levels Of Zyx Were Observed In Melanoma Cmentioning

confidence: 99%

The Role of Zyxin in Carcinogenesis

et al. 2020

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“…Strong focal adhesions (FA) are characteristic of the elongated mesenchymal invasive phenotype. Both N-glycosylation and zyxin upregulation (47,48) would suggest that YB-1 knock-out could also be prone to metastasize. Other strongly upregulated proteins included TGM2 which is a stress-responsive gene that encodes a multifunctional and structurally complex protein called tissue transglutaminase (TG2).…”

Section: Discussionmentioning

confidence: 99%

Biomechanical and biochemical assessment of YB-1 expression in melanoma cells

Cykowska

Hofmann

Tiwari³

et al. 2021

Preprint

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Malignant melanoma is the most lethal form of skin cancer; its incidence has increased over the last five decades. Y-box binding protein 1 (YB-1) plays a prominent role in mediating metastatic behavior by promoting epithelial-to-mesenchymal transition (EMT) processes. Migratory melanoma cells exhibit two major phenotypes: elongated mesenchymal or rounded amoeboid. The actomyosin cytoskeleton is key in both phenotypes, but intermediate filaments also undergo a significant rearrangement process, switching from cytokeratin-rich to vimentin and nestin-rich network. In this study, we aimed to investigate to what extent YB-1 impacts the biomechanical (cell stiffness) and biochemical aspects of melanoma cells and their cytoskeleton. To this end, we subjected A375 YB-1 knock-out and parental cells to atomic force microscopy investigations (stiffness determination), immunolabelling, and proteome analysis. We found that YB-1 expressing cells were significantly stiffer compared to the corresponding YB-1 knock-out cell line. Proteomic analysis revealed that expression of YB-1 results in a strong co-expression of nestin, vimentin, fascin-1, and septin-9. In the YB-1 knock-out nestin was completely depleted, but zyxin was strongly upregulated. Collectively, our results showed that YB-1 knock-out acquires some characteristics of mesenchymal phenotype but lacks important markers of malignancy and invasiveness such as nestin or vimentin. We posit that there is an association of YB-1 expression with an amoeboid phenotype, which would explain the increased migratory capacity.

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Zyxin as a potential cancer prognostic marker promotes the proliferation and metastasis of colorectal cancer cells

Cited by 18 publications

References 62 publications

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

The Role of Zyxin in Carcinogenesis

Biomechanical and biochemical assessment of YB-1 expression in melanoma cells

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