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<p>Prickle planar cell polarity protein 3 (PRICKLE3) is involved in tumor malignant progression. However, little information is available regarding its detailed mechanism in non-small cell lung cancer (NSCLC). The clinicopathological significance of PRICKLE3 in NSCLC specimens was assessed. PRICKLE3-overexpression and PRICKLE3-knockout NSCLC cells were generated in vivo and in vitro. The interaction among PRICKLE3, ubiquitin-specific peptidase 9, X-chromosome (USP9X) and dishevelled2 (DVL2) in NSCLC cells was identified. We found that PRICKLE3 overexpression was correlated with advanced TNM stage, lymphatic metastasis, and poor prognosis in NSCLC patients. PRICKLE3 knockdown inhibited the viability, colony formation, and invasiveness in A549 and H1299 cells, and its overexpression promoted the viability, colony formation, and invasiveness in HBE, H460, and LK2 cells. PRICKLE3 promoted NSCLC growth in vivo. PRICKLE3-DVL2 interaction enhanced the β-catenin phosphorylation at serine 675 for β-catenin nuclear translocation. Furthermore, PRICKLE3 interacted with USP9X to inhibit the DVL2 ubiquitination for the DVL2 stability and the activation of canonical WNT signaling. Overall, we demonstrate a novel signal transduction pathway where PRICKLE3 interacts with USP9X and DVL2 to enhance the DVL2 deubiquitination mediated by USP9X for stabilizing DVL2 expression and activate the canonical WNT signaling for promoting the NSCLC progression.</p><p></p>

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PRICKLE3-USP9X interaction-mediated DVL2 deubiquitination promotes the progression of non-small cell lung cancer via canonical WNT pathway

  • 期刊论文

  • 发表日期：

    2025年9月19日

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  • Mengdi Yang,
  • Yudie Lu,
  • Jingrong Zheng,
  • Xinran Zhao,
  • Guangping Wu,
  • Enhua Wang,
  • Huanyu Zhao

摘要

Prickle planar cell polarity protein 3 (PRICKLE3) is involved in tumor malignant progression. However, little information is available regarding its detailed mechanism in non-small cell lung cancer (NSCLC). The clinicopathological significance of PRICKLE3 in NSCLC specimens was assessed. PRICKLE3-overexpression and PRICKLE3-knockout NSCLC cells were generated in vivo and in vitro. The interaction among PRICKLE3, ubiquitin-specific peptidase 9, X-chromosome (USP9X) and dishevelled2 (DVL2) in NSCLC cells was identified. We found that PRICKLE3 overexpression was correlated with advanced TNM stage, lymphatic metastasis, and poor prognosis in NSCLC patients. PRICKLE3 knockdown inhibited the viability, colony formation, and invasiveness in A549 and H1299 cells, and its overexpression promoted the viability, colony formation, and invasiveness in HBE, H460, and LK2 cells. PRICKLE3 promoted NSCLC growth in vivo. PRICKLE3-DVL2 interaction enhanced the β-catenin phosphorylation at serine 675 for β-catenin nuclear translocation. Furthermore, PRICKLE3 interacted with USP9X to inhibit the DVL2 ubiquitination for the DVL2 stability and the activation of canonical WNT signaling. Overall, we demonstrate a novel signal transduction pathway where PRICKLE3 interacts with USP9X and DVL2 to enhance the DVL2 deubiquitination mediated by USP9X for stabilizing DVL2 expression and activate the canonical WNT signaling for promoting the NSCLC progression.