Functional roles of the SHCBP1 and KIF23 interaction in modulating the cell-cycle and cisplatin resistance of head and neck squamous cell carcinoma

Yonghong Sun; Haixia Pan; Yanwei He; Chunmei Hu; Yi Gu

doi:10.1002/hed.26961

Functional roles of the SHCBP1 and KIF23 interaction in modulating the cell-cycle and cisplatin resistance of head and neck squamous cell carcinoma

Head Neck. 2022 Mar;44(3):591-605. doi: 10.1002/hed.26961. Epub 2021 Dec 17.

Authors

Yonghong Sun¹, Haixia Pan², Yanwei He³, Chunmei Hu⁴, Yi Gu⁵

Affiliations

¹ Department of Oncology, Nanchong Central Hospital, Nanchong, China.
² Cancer Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁴ Department of Otolaryngology - Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁵ Department of Vascular and Thyroid Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

PMID: 34918847
DOI: 10.1002/hed.26961

Abstract

Background: This study aimed to explore the functional roles of Shc SH2-domain-binding protein 1 (SHCBP1) and Kinesin Family Member 23 (KIF23) in HPV-negative head and neck squamous cell carcinoma (HNSCC).

Methods: Bioinformatic analysis was conducted using data from The Cancer Genome Atlas (TCGA) and GSE103322. HNSCC cell lines were used for in vitro and in vivo analysis.

Results: SHCBP1 upregulation was associated with unfavorable survival. SHCBP1 knockdown reduced cell proliferation and increased the cisplatin sensitivity of SCC9/SCC25 cells. SHCBP1 interacted with KIF23 via its Nesd homology domain (NHD) domain, which was important for its nucleus localization. SHCBP1 positively modulated KIF23 expression and activated phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), extracellular signal regulated kinase (ERK)1/2, nuclear factor kappa B (NF/κB)-p65, and Wnt/β-catenin signaling. KIF23 knockdown abrogated cisplatin resistance induced by SHCBP1 overexpression.

Conclusion: SHCBP1 interacts with KIF23 and cooperatively regulates cell-cycle progression and cisplatin resistance of HNSCC tumor cells.

Keywords: ERK1/2; HNSCC; KIF23; SHCBP1; Wnt/β-catenin; cell-cycle.

Publication types

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

MeSH terms

Cell Line, Tumor
Cell Proliferation
Cisplatin* / pharmacology
Head and Neck Neoplasms* / drug therapy
Head and Neck Neoplasms* / genetics
Humans
Microtubule-Associated Proteins / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Shc Signaling Adaptor Proteins / genetics
Shc Signaling Adaptor Proteins / metabolism
Squamous Cell Carcinoma of Head and Neck

Substances

KIF23 protein, human
Microtubule-Associated Proteins
SHCBP1 protein, human
Shc Signaling Adaptor Proteins
Cisplatin