The primary obstacle to treat cervical cancer is its high prevalence of metastasis, which severely affects patients’ quality of life and survival time. Nucleolar and spindle associated protein 1 (NUSAP1) has been implicated in the development, progression, and metastasis in several types of cancer. However, its oncogenic role in cervical cancer remains unclear. Western blot assay and immunohistochemistry were used to determine the expression of NUSAP1 in 21 clinical fresh Cervical cancer tissues and 233 clinicopathologically characterized cervical cancer specimens. The biological roles of NUSAP1 in the metastasis of cervical cancer were investigated both in vitro by EMT, Side population analysis and Transwell assays and so on, and in vivo using a mouse 4w model of hematogenous metastasis and lymph node metastasis. Bioinformatics analysis, luciferase reporter analysis, immunoprecipitation and immunoblotting of nuclear and cytoplasmic cellular fractions were applied to discern and examine the relationshipbetween NUSAP1 and its potential targets. The results demonstrated that NUSAP1 was upregulated in cervical cancer cells and tissues, correlated positively with metastasis and poor clinical outcome of patients. High expression of NUSAP1 promoted metastasis by enhancing cancer stem cell (CSC) traits and epithelial-mesenchyme transition (EMT) progression, while silencing of NUSAP1 reduced CSC traits and EMT progression. Mechanistically, upregulation of NUSAP1 induced SUMOylation of TCF4 via interacting with SUMO E3 ligase Ran-binding protein 2 (RanBP2) and hyperactivated Wnt/β-catenin signaling in cervical cancer cells. Additionally, NUSAP1-induced cervical cancer cells metastasis and the cancer stem cell phenotype were abrogated with the Wnt/β-catenin signaling inhibitor XAV-939 treatment. Importantly, co-therapy of conventional treatment and XAV-939 will provide a novel and effective treatment for NUSAP1-ovexpressed cervical cancer patients. Our results demonstrate thatNUSAP1 upregulation contributes to metastasis of cervical cancer by promoting CSC properties and EMT via Wnt/β-catenin signaling and XAV-939 might serve as a potential tailored therapeutic option for patients with NUSAP1-ovexpressed cervical cancer.

Abnormal stress in cranial sutures is strongly related to deformational plagiocephaly (DP) and is responsible for morphological changes in the skull, facial asymmetry, and abnormal facial tension. To evaluate the effect of biomechanical therapy on cranial sutures of DP we performed in silico analysis of normal skull in the supine position (Model 1), DP in the supine position (Model 2), and DP wearing moulding helmet (Model 3). By utilizing 3D point cloud data, we generated finite element models (FEMs) and developed 14 cranial sutures. We evaluated the mechanical causes of the continuous progression of moderate to severe DP by comparing the Von Mises Stress (VMS) distributions of 14 cranial sutures between Model 1 and Model 2, and used the same method to compare Model 2 with Model 3 to determine the reasons for the alleviation of DP. When the DP wore a moulding helmet, the VMS on the compressed side of the cranial sutures was reduced, and the skull support site shifted to the contralateral side. DP was associated with abnormal stress accumulation on the compressed side of the cranial sutures. Balancing the forces on both sides of the lambdoid suture, allowing the skull to accept a larger force area and applying stress to the cranial sutures on the uncompressed side may be the mechanism for the prevention and treatment of DP. The asymmetry caused by DP may be associated with abnormal stress accumulation in cranial sutures, and eliminating abnormal stress accumulation in cranial sutures and applying stress to contralateral cranial sutures are key measures of treatment. The force distribution area of the moulding helmet and the degree of head position adjustment may serve as an early indicator for assessing the moulding helmet’s efficacy. Adding bilateral lambdoid suture support straps to the moulding helmet may be the key to improving the efficacy. Our study revealed that the mechanical principles of helmet therapy and osteopathic treatment may support the use of osteopathic treatment as a first-line approach for treating DP.