scholarly journals Molecular Activation of the Kv11.1 Channel Reprograms EMT in Colon Cancer by Inhibiting TGFβ Signaling via Activation of Calcineurin

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6025
Author(s):  
Najmeh Eskandari ◽  
Vitalyi Senyuk ◽  
Jennifer Moore ◽  
Zane Kalik ◽  
Qiyue Luan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Vital Role ◽  
Colon Cancer Cells ◽  
Strong Inhibition ◽  
Tgfβ Signaling ◽  
Mesenchymal Transition ◽  
Stimulation Of

Control of ionic gradients is critical to maintain cellular homeostasis in both physiological and pathological conditions, but the role of ion channels in cancer cells has not been studied thoroughly. In this work we demonstrated that activity of the Kv11.1 potassium channel plays a vital role in controlling the migration of colon cancer cells by reversing the epithelial-to-mesenchymal transition (EMT) into the mesenchymal-to-epithelial transition (MET). We discovered that pharmacological stimulation of the Kv11.1 channel with the activator molecule NS1643 produces a strong inhibition of colon cancer cell motility. In agreement with the reversal of EMT, NS1643 treatment leads to a depletion of mesenchymal markers such as SNAIL1, SLUG, TWIST, ZEB, N-cadherin, and c-Myc, while the epithelial marker E-cadherin was strongly upregulated. Investigating the mechanism linking Kv11.1 activity to reversal of EMT into MET revealed that stimulation of Kv11.1 produced a strong and fast inhibition of the TGFβ signaling. Application of NS1643 resulted in de-phosphorylation of the TGFβ downstream effectors R-SMADs by activation of the serine/threonine phosphatase PP2B (calcineurin). Consistent with the role of TGFβ in controlling cancer stemness, NS1643 also produced a strong inhibition of NANOG, SOX2, and OCT4 while arresting the cell cycle in G0/G1. Our data demonstrate that activation of the Kv11.1 channel reprograms EMT into MET by inhibiting TGFβ signaling, which results in inhibition of motility in colon cancer cells.

Role of SPARC in the epithelial mesenchymal transition induced by PTHrP in human colon cancer cells

2021 ◽  
pp. 111253
Author(s):  
Pedro Carriere ◽  
Natalia Calvo ◽  
María Belén Novoa ◽  
Fernanda Lopez-Moncada ◽  
Alexander Riquelme ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Human Colon Cancer Cells

scholarly journals Epithelial-to-Mesenchymal Transition is Induced in Colon Cancer Cells Carrying the D299G Allele of the TLR4 Gene

2011 ◽  
Vol 140 (5) ◽  
pp. S-132
Author(s):  
Annette Eyking ◽  
Birgit Ey ◽  
Michael W. Rünzi ◽  
Andres I. Roig ◽  
Guido Gerken ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Tlr4 Gene

scholarly journals Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽  
2015 ◽  
Vol 35 (24) ◽  
pp. 3151-3162 ◽  
Author(s):  
Q Zhang ◽  
T Wei ◽  
K Shim ◽  
K Wright ◽  
K Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

scholarly journals Natural Compound Shikonin Induces Apoptosis and Attenuates Epithelial to Mesenchymal Transition in Radiation-Resistant Human Colon Cancer Cells

2021 ◽  
Author(s):  
Kristina Shilnikova ◽  
Mei Jing Piao ◽  
Kyoung Ah Kang ◽  
Pincha Devage Sameera Madushan Fernando ◽  
Herath Mudiyanselage Udari Lakmini Herath ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Natural Compound ◽  
Epithelial To Mesenchymal Transition ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Radiation Resistant ◽  
Human Colon Cancer Cells
Sign in / Sign up

Export Citation Format

Share Document