Wnt/PCP pathway and extracellular matrix mechanical signaling regulating CNN2 to promote collective migration of hepatocellular carcinoma cells
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1Hepatobiliary Center,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029 ; 2.Breast Center,Zhongda Hospital Affiliated to Southeast University,Nanjing 210009 ,China

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    Abstract:

    Objective:To investigate the effects and molecular mechanisms in Wnt/PCP signaling pathway and extracellular matrix (ECM)collaboratively regulating calponin-2(CNN2)to drive collective migration in hepatocellular carcinoma(HCC)cells. Methods: The expression characteristics of CNN2 across various tissues were analyzed by integrating data from The Cancer Genome Atlas (TCGA)and the Human Protein Atlas(HPA). Its expression level and prognostic relevance in HCC were further evaluated using tissue microarrays. To investigate the functional role of CNN2 in cell migration,transwell and wound healing assays were performed. Furthermore,shRNA - lentivirus mediated knockdown of Wnt11 and CNN2 was employed to elucidate the regulatory relationship between the Wnt/PCP signaling pathway and CNN2,as well as the underlying molecular mechanisms. Finally,rigid substrates was used to mimic the ECM environment,aiming to explore its association with CNN2 expression and the migratory capacity of HCC cells. Results:CNN2 was highly expressed in HCC tissues and was predominantly enriched at the invasive tumor front,suggesting a potential role in the early stages of tumor cell migration. Functional assays further demonstrated that CNN2 significantly promoted collective migration of HCC cells,and its high expression was markedly associated with poor patient prognosis. Mechanistically,CNN2 was regulated by the Wnt/PCP signaling pathway,and its expression was notably upregulated under conditions simulating the mechanical properties of the ECM,indicating a critical role in the cellular perception and response to biomechanical signal. Conclusion:The Wnt/PCP signaling pathway regulates the expression and function of CNN2,while CNN2,as a mediator of mechanical signals,is regulated by ECM mechanical signals. Together,they synergistically drive the collective migration of HCC cells.

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TAO Zifan, LIU Yiwei, WU Xiaofeng, YU Yue. Wnt/PCP pathway and extracellular matrix mechanical signaling regulating CNN2 to promote collective migration of hepatocellular carcinoma cells[J].,2025,(7):936-944.

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  • Received:March 12,2025
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  • Online: July 10,2025
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