Phenotypic Plasticity of Cutaneous Squamous Cell Carcinoma Mediated by Cyclooxygenase-2

Abstract

A method and server for predicting damaging missense mutations. Nat Methods 2010;7: 248e9.

New insights into the functions of Cox-2 in skin and esophageal malignancies

“…However, the same stem cell populations with a lack of Cox-2 expression tend to form less aggressive or typical epithelial-type SCCs (in contrast to spindle-type SCCs) that are typically well demarcated from the dermis. Together with previous studies [56][57][58][59][60] , this study 62 demonstrates that Cox-2 expression acts as a tumor promoter that is both required for efficient tumor formation and involved in determining the subtype of cutaneous SCC tumors from the same cancer cells of origin (summary of cell-type-specific Cox-2 expression in cutaneous SCC in Fig. 1b).…”

“…Similarly, cell-type-specific Cox-2 knockout in Krt14-Cre + epidermal basal cells significantly suppressed UV-mediated tumor formation in mouse skin 60 . Using a Cox-2 conditional knockout model (Ptgs2 flox/flox ) developed by the Herschman group 61 , we have also recently determined the role of cell-type-specific Cox-2 expression in Krt15-CrePR + tumor-prone hair follicle stem cells expressing Kras G12D together with a p53 loss of function mutation 62 . Cox-2 is known to regulate the Akt-mTOR pathway, which is also required for efficient cutaneous wound healing 63,64 .…”

“…Additionally, Cox-2 inhibition could have suppressive effects on the development of tumors from mutant hair follicle stem cells, as Akt pathway activation enhances SCC formation 41 . Intriguingly, genetic inhibition of Cox-2 suppressed tumor development and inhibited EMT-like properties during tumorigenesis 62 . Oncogenic Ras/p53 expression significantly and directly induces invasive, mesenchymal-like SCC formation from Krt15-positive stem cells, which tend to show loss of epithelial markers (e.g., E-cad) but overexpression of mesenchymal markers (e.g., vimentin and N-cad) 21,23 .…”

“…Additionally, lineage tracing of tumor-susceptible stem cells may further provide data regarding the control of tumor-prone stem cell fate. Genetically engineered mouse models of both cutaneous 62 and esophageal SCCs 74 have demonstrated that Cox-2 inhibition promotes a more well-or moderately differentiated phenotype than high levels of Cox-2. A lack or low levels of differentiation are hallmarks of cancers with poorly differentiated phenotypes and poor prognosis.…”

Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review)

“…In addition, COX-2 can modulate the actions of the immune system by constitutively upregulating indoleamine 2,3-dioxygenase 1 expression in human tumor cells (45). However, COX-2 knockdown significantly suppresses the degree of differentiation in genetically modified mice bearing cutaneous cancer (46) and esophageal cancer (47). Notably, the lack of differentiation is an important hallmark of cancer cells (17).…”