Cargando…

ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness

Ectodermal neural cortex 1 (ENC1) is an actin-binding protein and has been known to be upregulated in several cancers, but the molecular mechanisms through which it contributes to the pathology of CRC have largely been elusive. We utilized data mining and validated the aberrant expression of ENC1, f...

Descripción completa

Detalles Bibliográficos
Autores principales: Cui, Ying, Yang, Jiani, Bai, Yibing, Li, QingWei, Yao, Yuanfei, Liu, Chao, Wu, Feng, Zhang, Jingchun, Zhang, Yanqiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010667/
https://www.ncbi.nlm.nih.gov/pubmed/33816464
http://dx.doi.org/10.3389/fcell.2021.616887
_version_ 1783673103770976256
author Cui, Ying
Yang, Jiani
Bai, Yibing
Li, QingWei
Yao, Yuanfei
Liu, Chao
Wu, Feng
Zhang, Jingchun
Zhang, Yanqiao
author_facet Cui, Ying
Yang, Jiani
Bai, Yibing
Li, QingWei
Yao, Yuanfei
Liu, Chao
Wu, Feng
Zhang, Jingchun
Zhang, Yanqiao
author_sort Cui, Ying
collection PubMed
description Ectodermal neural cortex 1 (ENC1) is an actin-binding protein and has been known to be upregulated in several cancers, but the molecular mechanisms through which it contributes to the pathology of CRC have largely been elusive. We utilized data mining and validated the aberrant expression of ENC1, following which phenotypic traits of malignancy were assessed in vitro. Ruxolitinib was used as a surrogate to compare the effects of ENC1 expression and silencing on the JAK-STAT-AKT pathway. In vivo models were employed to confirm the in vitro observations. Computation analysis, strengthened by in situ and in vitro data, confirmed the overexpression of ENC1 in CRC and predicted a poor prognosis, while enhanced cell proliferation, invasion, migration, EMT, and stemness were associated with ENC1 overexpression. Silencing of ENC1 downregulated the phenotypes. Additionally, silencing of ENC1 significantly reduced the activation of JAK2 and consequent activation of STAT5 and AKT comparable to ruxolitinib inhibition of JAK2. Silencing of ENC1 resulted in lesser tumor volumes and fewer numbers of tumors, in vivo. These data suggest that ENC1 induces CRC through the JAK2-STAT5-AKT axis. ENC1 is a suitable diagnostic marker for CRC detection, and ENC1 targeting therapies may suppress CRC progression.
format Online
Article
Text
id pubmed-8010667
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-80106672021-04-01 ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness Cui, Ying Yang, Jiani Bai, Yibing Li, QingWei Yao, Yuanfei Liu, Chao Wu, Feng Zhang, Jingchun Zhang, Yanqiao Front Cell Dev Biol Cell and Developmental Biology Ectodermal neural cortex 1 (ENC1) is an actin-binding protein and has been known to be upregulated in several cancers, but the molecular mechanisms through which it contributes to the pathology of CRC have largely been elusive. We utilized data mining and validated the aberrant expression of ENC1, following which phenotypic traits of malignancy were assessed in vitro. Ruxolitinib was used as a surrogate to compare the effects of ENC1 expression and silencing on the JAK-STAT-AKT pathway. In vivo models were employed to confirm the in vitro observations. Computation analysis, strengthened by in situ and in vitro data, confirmed the overexpression of ENC1 in CRC and predicted a poor prognosis, while enhanced cell proliferation, invasion, migration, EMT, and stemness were associated with ENC1 overexpression. Silencing of ENC1 downregulated the phenotypes. Additionally, silencing of ENC1 significantly reduced the activation of JAK2 and consequent activation of STAT5 and AKT comparable to ruxolitinib inhibition of JAK2. Silencing of ENC1 resulted in lesser tumor volumes and fewer numbers of tumors, in vivo. These data suggest that ENC1 induces CRC through the JAK2-STAT5-AKT axis. ENC1 is a suitable diagnostic marker for CRC detection, and ENC1 targeting therapies may suppress CRC progression. Frontiers Media S.A. 2021-03-16 /pmc/articles/PMC8010667/ /pubmed/33816464 http://dx.doi.org/10.3389/fcell.2021.616887 Text en Copyright © 2021 Cui, Yang, Bai, Li, Yao, Liu, Wu, Zhang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Cui, Ying
Yang, Jiani
Bai, Yibing
Li, QingWei
Yao, Yuanfei
Liu, Chao
Wu, Feng
Zhang, Jingchun
Zhang, Yanqiao
ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness
title ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness
title_full ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness
title_fullStr ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness
title_full_unstemmed ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness
title_short ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness
title_sort enc1 facilitates colorectal carcinoma tumorigenesis and metastasis via jak2/stat5/akt axis-mediated epithelial mesenchymal transition and stemness
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010667/
https://www.ncbi.nlm.nih.gov/pubmed/33816464
http://dx.doi.org/10.3389/fcell.2021.616887
work_keys_str_mv AT cuiying enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT yangjiani enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT baiyibing enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT liqingwei enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT yaoyuanfei enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT liuchao enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT wufeng enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT zhangjingchun enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness
AT zhangyanqiao enc1facilitatescolorectalcarcinomatumorigenesisandmetastasisviajak2stat5aktaxismediatedepithelialmesenchymaltransitionandstemness