KCTD12 Regulates Colorectal Cancer Cell Stemness through the ERK Pathway

Liping Li, Tingmei Duan, Xin Wang, Ru Hua Zhang, Meifang Zhang, Suihai Wang, Fen Wang, Yuanzhong Wu, Haojie Huang, Tiebang Kang

Research output: Contribution to journalArticle

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Abstract

Targeting cancer stem cells (CSCs) in colorectal cancer (CRC) remains a difficult problem, as the regulation of CSCs in CRC is poorly understood. Here we demonstrated that KCTD12, potassium channel tetramerization domain containing 12, is down-regulated in the CSC-like cells of CRC. The silencing of endogenous KCTD12 and the overexpression of ectopic KCTD12 dramatically enhances and represses CRC cell stemness, respectively, as assessed in vitro and in vivo using a colony formation assay, a spheroid formation assay and a xenograft tumor model. Mechanistically, KCTD12 suppresses CRC cell stemness markers, such as CD44, CD133 and CD29, by inhibiting the ERK pathway, as the ERK1/2 inhibitor U0126 abolishes the increase in expression of CRC cell stemness markers induced by the down-regulation of KCTD12. Indeed, a decreased level of KCTD12 is detected in CRC tissues compared with their adjacent normal tissues and is an independent prognostic factor for poor overall and disease free survival in patients with CRC (p = 0.007). Taken together, this report reveals that KCTD12 is a novel regulator of CRC cell stemness and may serve as a novel prognostic marker and therapeutic target for patients with CRC.

Original languageEnglish (US)
Article number20460
JournalScientific Reports
Volume6
DOIs
StatePublished - Feb 5 2016

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MAP Kinase Signaling System
Colorectal Neoplasms
Neoplastic Stem Cells
Xenograft Model Antitumor Assays
Potassium Channels
Disease-Free Survival
Down-Regulation

ASJC Scopus subject areas

  • General

Cite this

Li, L., Duan, T., Wang, X., Zhang, R. H., Zhang, M., Wang, S., ... Kang, T. (2016). KCTD12 Regulates Colorectal Cancer Cell Stemness through the ERK Pathway. Scientific Reports, 6, [20460]. https://doi.org/10.1038/srep20460

KCTD12 Regulates Colorectal Cancer Cell Stemness through the ERK Pathway. / Li, Liping; Duan, Tingmei; Wang, Xin; Zhang, Ru Hua; Zhang, Meifang; Wang, Suihai; Wang, Fen; Wu, Yuanzhong; Huang, Haojie; Kang, Tiebang.

In: Scientific Reports, Vol. 6, 20460, 05.02.2016.

Research output: Contribution to journalArticle

Li, L, Duan, T, Wang, X, Zhang, RH, Zhang, M, Wang, S, Wang, F, Wu, Y, Huang, H & Kang, T 2016, 'KCTD12 Regulates Colorectal Cancer Cell Stemness through the ERK Pathway', Scientific Reports, vol. 6, 20460. https://doi.org/10.1038/srep20460
Li, Liping ; Duan, Tingmei ; Wang, Xin ; Zhang, Ru Hua ; Zhang, Meifang ; Wang, Suihai ; Wang, Fen ; Wu, Yuanzhong ; Huang, Haojie ; Kang, Tiebang. / KCTD12 Regulates Colorectal Cancer Cell Stemness through the ERK Pathway. In: Scientific Reports. 2016 ; Vol. 6.
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