Co-opted JNK/SAPK signaling in Wnt/beta-catenin-induced tumorigenesis.

Neoplasia : an International Journal for Oncology Research
Bo LiuWei Hsu

Abstract

Aberrant stimulation of the canonical Wnt pathway induces mammary tumorigenesis in mice. It has been well documented that two types of tumors, adenocarcinoma and adenocarcinoma with squamous metaplasia, develop in these mutants. However, the molecular mechanism underlying the induction of squamous transdifferentiation remains largely unknown. Here, we show that JNK/SAPK signaling plays an important role in Wnt-dependent mammary development and malignant transformation. The JNK/SAPK pathway is stimulated in pregnancy-mediated lobulo-alveolar morphogenesis, a process highly dependent on Wnt/beta-catenin signaling. Strong elevations of JNK/SAPK signaling are associated with squamous metaplasia of the Wnt-induced adenocarcinoma. Reconstitution of beta-catenin and JNK/SAPK signaling activities also promotes expression of the squamous cell marker in cultured epithelial cells. Furthermore, a synergistic activation of these two pathways can be identified in the malignant squamous cells of human endometrial and lung cancers. This is potentially a significant discovery in modern cancer therapy because of the effectiveness of an angiogenesis inhibitor, Avastin, for the treatment of adenocarcinoma, but not squamous cell carcinoma, in human...Continue Reading

Citations

Jun 16, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Hsiao-Man Ivy YuWei Hsu
May 19, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Takamitsu MaruyamaWei Hsu
Jan 20, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jiang FuWei Hsu
Jan 5, 2012·PloS One·Jenifer R ProsperiKathleen H Goss
Oct 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jiang FuWei Hsu
Nov 29, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Takamitsu MaruyamaWei Hsu
Dec 25, 2010·Cell Death and Differentiation·M JiangW Hsu
Aug 5, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Wei HsuHsiao-Man Ivy Yu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.