Downregulation of keratins 8, 18 and 19 influences invasiveness of human cultured squamous cell carcinoma and adenocarcinoma cells

AbstractWhile the class I of PI3Ks has been deeply studied due to its clear implication in cancer development, little is known about the class II of PI3Ks. However, recent accumulation of data is now revealing that PI3KC2β, one isoform of this class of PI3Ks, may also play a role in cancer. Specifically, recent studies have suggested an implication of PI3KC2β in metastasis formation through the promotion of epithelial to mesenchymal transition (EMT). Here, we report that the overexpression of PI3KC2β in the epidermal squamous cell carcinoma (ESCC) cells A431 promotes apparent EMT transformation. We further confirm this EMT by showing modification in several biochemical markers (E-cadherin, β-catenin, Snail, Twist1 and Vimentin). Furthermore, an intracellular co-localization of E-cadherin, β-catenin and EGFR was observed. This transformation decreased EGFR signaling and the sensitivity to inhibitors targeting this receptor. To confirm our results, we have used the colon adenocarcinoma cells HT29 and induced overexpression of PI3KC2β in these cells. We could recapitulate in this model some of our major findings regarding EMT in the PI3KC2β overexpressing A431 cells. Taken together, these data support a role of PI3KC2β in promoting EMT.

Download Full-text

E47 upregulates ΔNp63α to promote growth of squamous cell carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-03662-3 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Jing Xu ◽

Fengtian Li ◽

Ya Gao ◽

Rongtian Guo ◽

Liangping Ding ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

Drug Targets ◽

Clinical Samples ◽

Promote Cell Proliferation ◽

Adenocarcinoma Cells ◽

Poor Outcomes

AbstractTargeted therapy has greatly improved both survival and prognosis of cancer patients. However, while therapeutic treatment of adenocarcinoma has been advanced greatly, progress in treatment of squamous cell carcinoma (SCC) has been slow and ineffective. Therefore, it is of great importance to decipher mechanisms and identify new drug targets involved in squamous cell carcinoma development. In this study, we demonstrate that E47 plays the distinctive and opposite roles on cell proliferation in adenocarcinoma and squamous cell carcinoma. While E47 suppresses cell proliferation in adenocarcinoma cells, it functions as a oncoprotein to promote cell proliferation and tumor growth of squamous cell carcinoma. Mechanistically, we show that E47 can directly bind to the promoter and transactivate ΔNp63 gene expression in squamous cell carcinoma cells, resulting in upregulation of cyclins D1/E1 and downregulation of p21, and thereby promoting cell proliferation and tumor growth. We further show that expression of E2A (E12/E47) is positively correlated with p63 and that high expression of E2A is associated with poor outcomes in clinical samples of squamous cell carcinoma. These results highlight that the E47-ΔNp63α axis may be potential therapeutic targets for treatment of squamous cell carcinoma.

Download Full-text