Induction of squamous cell carcinoma after MAP3K8 overexpression in murine salivry gland epithelial cells

Abstract

Background Salivary gland neoplasms are relatively rare and comprise only 1%‐4% of all human neoplasms. Salivary gland neoplasms also show an extremely wide range of morphological diversity. Currently, the genetic alterations and corresponding molecular mechanisms underlying salivary gland neoplasms development remain largely unknown. Method We generated an inducible Tet‐MAP3K8::MMTV‐rTA mouse model by crossing the MAP3K8 transgenic mice with MMTR‐rTA transgenic mice to express MAP3K8 in the salivary gland. Results MAP3K8 overexpression in the murine salivary glands of Tet‐MAP3K8::MMTR‐rTA transgenic mice induces tumorigenesis. Pathological investigations reveal partial fibrosis and adenosis of salivary glands, and foci of atypical squamoid cellular proliferation, which represent invasive squamous cell carcinoma (SCC). Conclusion MAP3K8 overexpression is associated with SCC development in murine salivary glands. It provides an in vivo framework for the understanding of molecular mechanisms underlying SCC development in the salivary glands and also for the development of a future therapeutic strategy targeting this tumor type.

RETRACTED: LncRNA LIPE-AS1 Predicts Poor Survival of Cervical Cancer and Promotes Its Proliferation and Migration via Modulating miR-195-5p/MAPK Pathway

“…Among multiple tumors, mitogen-activated protein kinase kinase kinase 8 (MAP3K8) is closely related to the malignant biological behavior of tumors and promotes the development of melanoma (10), squamous cell carcinoma (11), and other tumors. In the meantime, several miRNAs are found to target MAP3K8.…”

Characterization of macrophages in head and neck squamous cell carcinoma and development of MRG-based risk signature

“…In this study, AQP1, ITGA5, MAP3K8, PIK3R3, STC1 and TGM2 were significantly overexpressed in HNSCC tumor tissues, while SH2D3C expression was significantly reduced, and there was no difference in ARHGAP4 expression. This is similar to the results of "Guo et al found that AQP1 can promote local invasion of breast cancer, Xu et al found that ITGA5 can promote angiogenesis in cervical cancer, and Lee et al found that MAP3K8 overexpression can induce squamous cell carcinogenesis in the salivary glands of mice" 78 – 80 . Studies have shown that STC1 is not only one of MRGs, but also a glycolysis-related genes in HNSCC, which is prominently expressed in the glycolytic activities of tumor tissues and can also predict the prognosis of HNSCC from the direction of glycolysis, which is similar to the conclusion of this study 81 .…”

Novel ferroptosis signature for improving prediction of prognosis and indicating gene targets from single-cell level in oral squamous cell carcinoma

“…In addition, MAP3K8 overexpression is linked to OSCC development in murine salivary glands. Therefore, KIN001-266, as an inhibitor of MAP3K8, has potential inhibitory effects on OSCC [ 37 ].To date, no studies have explored the effects of 5Z)-7-Oxozeaenol, AT-7519, and KIN001-266 on OSCC. Therefore, this study provides novel insights and avenues for further investigation into patient-specific chemotherapy regimens for the treatment of OSCC.…”