Wnt5a regulates Ameloblastoma Cell Migration by modulating Mitochondrial and Cytoskeletal Dynamics

Abstract

Objective: Abnormal expression of Wnt5a has been detected in various tumors, including ameloblastoma (AB). Yet, there is no specific mechanistic evidence for the functional role of Wnt5a in AB. In this study, we aimed to conduct a mechanistic examination of the importance of Wnt5a in AB development. Methods: The expressions of Wnt5a and Coro1A were examined by Western blot and immunohistochemistry both in AB tissues and AM-1 cells. The number and size of mitochondria were detected by electronic transmission microscope and confocal microscope. Gain-of-function and loss-of-function assays were used to explore the biological roles of Wnt5a and Coro1A in organelle dynamics changes and cell migration. Cell migration was detected by wound healing and transwell assay. Results: We found that in AM-1 cells, up-regulation of Wnt5a led to enhanced mitochondrial energy production and altered calcium homeostasis, with elevated calcium levels directly leading to altered mitochondrial dynamics and interactions between the cytoskeleton and the mitochondria. When Wnt5a or its downstream cytoskeleton-associated protein Coro1A was knocked down, the migration capacity of AM-1 cells was markedly impaired. Conclusion: Together, these results suggest that Wnt5a plays mitochondria and cytoskeleton specific roles in regulating the development of human AB, with its down-regulation leading to impaired tumor development, thus highlighting Wnt5a or Coro1A as potentially viable therapeutic targets for the treatment of AB.

Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming

“…Previous research has demonstrated that Sal B may restrain the migration and invasion of hepatocellular carcinoma through RECK/STAT3 signaling [ 28 ]. For crossing the basement membrane along with the basal layer, tumor cells are functionally and morphologically altered through activating EMT that has the features of upregulation of β -cadherin and downregulation of E-cadherin [ 29 ]. Sal B administration enabled the decrease β -cadherin expression as well as the enhancement of E-cadherin expression of NCI-H2030 and NCI-H1650 cells, demonstrating the inactivation of EMT in NSCLC cells.…”

Interleukin‐1α promotes matrix metalloproteinase‐9 expression, cellular motility, and local invasiveness of ameloblastoma cells

“…These phenomena are consistent with the pathological finding of ameloblastoma cells invading the stroma and bone, similar to tuft formation. Recently, BRAF and Wnt signals were reported to contribute to the cell proliferation and migration of ameloblastoma cells, respectively 33–35 . Our findings suggested that IL‐1α might be the novel therapeutic target of ameloblastoma in addition to these molecules.…”

“…Recently, BRAF and Wnt signals were reported to contribute to the cell proliferation and migration of ameloblastoma cells, respectively. [33][34][35] Our findings suggested that IL-1α might be the novel therapeutic target of ameloblastoma in addition to these molecules.…”

TRIM11 Posttranscriptionally Modulated by miR-5193 Facilitates Tumor Growth and Metastasis of Prostate Cancer

“…3,43,44 Migration and invasion of tumor cells represent two crucial biological phenomena during metastases. 45,46 Herein, loss of TRIM11 decreased the migratory and invasive capacities of prostate cancer cells. In line with our experimental data, several researchers have determined that TRIM11 is correlated to migration and invasion in several human cancers.…”