Naa10p and IKKα interaction regulates EMT in oral squamous cell carcinoma via TGF-β1/Smad pathway

Sai Lv; Ting Luo; Yongyong Yang; Yuqing Li; Jie Yang; Jiang Xu; Jun Zheng; Yan Zeng

doi:10.1111/jcmm.16680

Naa10p and IKKα interaction regulates EMT in oral squamous cell carcinoma via TGF-β1/Smad pathway

J Cell Mol Med. 2021 Jul;25(14):6760-6772. doi: 10.1111/jcmm.16680. Epub 2021 May 31.

Authors

Sai Lv^{1

2}, Ting Luo¹, Yongyong Yang³, Yuqing Li⁴, Jie Yang^{1

2}, Jiang Xu^{1

2}, Jun Zheng^{1

2}, Yan Zeng^{1

2}

Affiliations

¹ Key Laboratory of Xinjiang Endemic and Ethnic Disease, School of Medicine, Shihezi University, Shihezi, China.
² Department of Stomatology, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China.
³ Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁴ Department of Urological Surgery, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, China.

Abstract

Epithelial-mesenchymal transition (EMT) has been contributed to increase migration and invasion of cancer cells. However, the correlate of Naa10p and IKKα with EMT in oral squamous cell carcinoma (OSCC) is not yet fully understood. In our present study, we found N-α-acetyltransferase 10 protein (Naa10p) and IκB kinase α (IKKα) were abnormally abundant in oral squamous cell carcinoma (OSCC). Bioinformatic results indicate that the expression of Naa10p and IKKα is correlated with TGF-β1/Smad and EMT-related molecules. The Transwell migration, invasion, qRT-PCR and Western blot assay indicated that Naa10p repressed OSCC cell migration, invasion and EMT, whereas IKKα promoted TGF-β1-mediated OSCC cell migration, invasion and EMT. Mechanistically, Naa10p inhibited IKKα activation of Smad3 through the interaction with IKKα directly in OSCC cells after TGF-β1 stimulation. Notably, knockdown of Naa10p reversed the IKKα-induced change in the migration, invasion and EMT-related molecules in OSCC cells after TGF-β1 stimulation. These findings suggest that Naa10p interacted with IKKα mediates EMT in OSCC cells through TGF-β1/Smad, a novel pathway for preventing OSCC.

Keywords: EMT; IKKα; Naa10p; OSCC; TGF-β1/Smad.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Cell Movement
Epithelial-Mesenchymal Transition*
Female
Humans
I-kappa B Kinase / genetics
I-kappa B Kinase / metabolism*
Male
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology
N-Terminal Acetyltransferase A / genetics
N-Terminal Acetyltransferase A / metabolism*
N-Terminal Acetyltransferase E / genetics
N-Terminal Acetyltransferase E / metabolism*
Protein Binding
Signal Transduction
Smad Proteins / metabolism
Transforming Growth Factor beta / metabolism

Substances

Smad Proteins
Transforming Growth Factor beta
N-Terminal Acetyltransferase A
NAA10 protein, human
N-Terminal Acetyltransferase E
CHUK protein, human
I-kappa B Kinase