E-cadherin knockdown increases β-catenin reducing colorectal cancer chemosensitivity only in three-dimensional cultures

International Journal of Oncology
Xi LiangJianming He

Abstract

Decreased expression of E-cadherin correlates with poor prognosis in colorectal cancer. Certain E-cadherin signaling cascades are triggered by intercellular force or binding to cadherins on adjacent cells. Three-dimensional (3D) cell cultures represent a better approximation of cell-cell adhesion in vivo than two-dimensional (2D) cultures. Here, we explored the role of E-cadherin in colorectal cancer chemosensitivity in 3D cultures. Cell-cell junctions, including tight junctions, gap junctions, intermediate junctions and desmosomes, were commonly found in 3D cultures. Knockdown of E-cadherin by lentiviral delivery of shRNA significantly reduced chemosensitivity to 5-fluorouracil and irinotecan, increased β-catenin protein level in HCT116 3D cultures. However, these effects were not observed in 2D cultures. Knockdown of β-catenin significantly increased chemosensitivity to 5-fluorouracil and irinotecan in HCT116 3D cultures and LoVo 3D cultures. 5-Fluorouracil activated p38, ERK1/2 and JNK1/2 in a time-dependent manner in HCT116 3D cultures. E-cadherin knockdown enhanced p-p38 and p-ERK1/2, except p-JNK1/2 in HCT116 3D cultures. Knockdown of β-catenin attenuated p-p38 and p-ERK1/2 in HCT116 3D cultures and LoVo 3D cultures. Inhi...Continue Reading

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Citations

Dec 7, 2017·Journal of the American Society for Mass Spectrometry·Xin LiuAmanda B Hummon
Jun 6, 2018·Cell Death and Differentiation·Chenming WuJian Yuan
May 27, 2021·Journal of Cellular Biochemistry·Ming-Cheng ChenChih-Yang Huang

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