p120‐catenin suppresses proliferation and tumor growth of oral squamous cell carcinoma via inhibiting nuclear phospholipase C‐γ1 signaling

Abstract

p120‐catenin (p120) serves as a stabilizer of the calcium‐dependent cadherin‐catenin complex and loss of p120 expression has been observed in several types of human cancers. The p120‐dependent E‐cadherin‐β‐catenin complex has been shown to mediate calcium‐induced keratinocyte differentiation via inducing activation of plasma membrane phospholipase C‐γ1 (PLC‐γ1). On the other hand, PLC‐γ1 has been shown to interact with phosphatidylinositol 3‐kinase enhancer in the nucleus and plays a critical role in epidermal growth factor‐induced proliferation of oral squamous cell carcinoma (OSCC) cells. To determine whether p120 suppresses OSCC proliferation and tumor growth via inhibiting PLC‐γ1, we examined effects of p120 knockdown or p120 and PLC‐γ1 double knockdown on proliferation of cultured OSCC cells and tumor growth in xenograft OSCC in mice. The results showed that knockdown of p120 reduced levels of PLC‐γ1 in the plasma membrane and increased levels of PLC‐γ1 and its signaling in the nucleus in OSCC cells and OSCC cell proliferation as well as xenograft OSCC tumor growth. However, double knockdown of p120 and PLC‐γ1 or knockdown of PLC‐γ1 alone did not have any effect. Immunohistochemical analysis of OSCC tissue from patients showed a lower expression level of p120 and a higher expression level of PLC‐γ1 compared with that of adjacent noncancerous tissue. These data indicate that p120 suppresses OSCC cell proliferation and tumor growth by inhibiting signaling mediated by nuclear PLC‐γ1.

Vitamin D receptor regulates proliferation and differentiation of thyroid carcinoma via the E-cadherin-β-catenin complex

“…Real-time PCR assays were carried out using the SYBR® Premix DimerEraserTMKit and specific primers. Quantitative real-time PCR (qRT-PCR) was performed according to the manufacturer’s instructions as previously described ( Li et al 2020 ). Data were analyzed by the instrument’s software and were normalized for GAPDH gene levels by the ΔΔCt method.…”

“…Six-week-old female severe combined immunodeficient (SCID) mice were purchased from Hunan Slac Laboratory Animal Company and were acclimated for 1 week in specific pathogen-free conditions. To assess the tumorigenicity of cells, the tumor-bearing mice model was conducted as described ( Li et al 2020 ). A total number of 5 × 10 6 cells were trypsinized and resuspended in PBS and then injected subcutaneously into the left or right rear flank of six SCID mice.…”

“…The tumor tissues were resected, photographed, weighed, and flash-frozen in liquid nitrogen and tainted with histology and immunohistochemistry to determine the expression levels of VDR, proliferating cell nuclear anitgen (PCNA), Ki67, BrdU, TPO, and TSHR. Slides were viewed and photographed under a light microscope (Olympus DP72) as described previously ( Li et al 2020 ). Animal handling and experimental procedures complied with guidelines established by the Animal Care and Use Committee of The Second Xiangya Hospital, Central South University.…”

Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis

“…Several findings demonstrated that the involvement of the PLC-γ1 pathway in Trks activation is crucial for the induction and maintenance of synaptic plasticity [ 35 ]. In addition, PLC-γ1 influences key cellular processes, such as proliferation and differentiation, in both neuronal and non-neuronal cells [ 6 , 36 , 37 , 38 , 39 , 40 ]. The activation of Ras pathway requires the NT binding to Trk receptors, their phosphorylation at Tyr490 residue and the subsequent recruitment/phosphorylation of the adaptor protein Shc.…”

Overexpression of PTPRZ1 Regulates p120/ β -Catenin Phosphorylation to Promote Carcinogenesis of Oral Submucous Fibrosis

“…PTPRZ1 has an important impact on the survival of OSCC patients, and the risk of death within 5 years of positive PTPRZ1 patients is 8 times lower than that of patients with negative PTPRZ1 [ 30 ]. Knockdown of P120 promotes OSCC cell proliferation and tumor growth through C- γ 1 signal transduction [ 31 ]. p-p120 promotes the progression and invasion of OSCC cells and may be a potential marker of OSCC disease [ 16 ].…”