CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma

Yuehong Shen; Yuling Chen; Yuntao Lin; Yicun Li; Pengfei Liu; Biru Zhang; Yufan Wang; King-Chi Chan; Nai-Ki Mak; Michael Kahn; Robert Z Qi; Hongyu Yang

doi:10.1038/s41419-023-05652-z

CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma

Cell Death Dis. 2023 Feb 11;14(2):107. doi: 10.1038/s41419-023-05652-z.

Authors

Yuehong Shen^{1

2}, Yuling Chen¹, Yuntao Lin¹, Yicun Li¹, Pengfei Liu², Biru Zhang^{1

3}, Yufan Wang¹, King-Chi Chan⁴, Nai-Ki Mak⁵, Michael Kahn⁶, Robert Z Qi^{7

8}, Hongyu Yang⁹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Stomatological Center, Peking University Shenzhen Hospital; Guangdong Provincial High-level Clinical Key Specialty; Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment; The Institute of Stomatology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong, China.
² Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
³ Department of Stomatology, Shenzhen Luohu People's Hospital, Guangdong, China.
⁴ Centre for PanorOmic Sciences, The University of Hong Kong, Hong Kong, China.
⁵ Department of Biology, Hong Kong Baptist University, Hong Kong, China.
⁶ Department of Molecular Medicine, City of Hope, Beckman Research Institute, Duarte, CA, USA.
⁷ Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China. qirz@ust.hk.
⁸ Bioscience and Biomedical Engineering Thrust, Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangdong, China. qirz@ust.hk.
⁹ Department of Oral and Maxillofacial Surgery, Stomatological Center, Peking University Shenzhen Hospital; Guangdong Provincial High-level Clinical Key Specialty; Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment; The Institute of Stomatology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong, China. hyyang192@hotmail.com.

Abstract

In oral squamous cell carcinoma (OSCC), a highly aggressive and frequently lethal malignancy, the role and action mechanism of the microtubule regulatory protein CDK5RAP2 have not been fully understood. Here, we show that CDK5RAP2 is highly expressed in OSCC and its expression correlates with clinical stage and lymph node metastasis of the disease. The expression of CDK5RAP2 is regulated by the Wnt signaling pathway. Depletion of CDK5RAP2 inhibits the tumorigenesis and migration of OSCC cells and alters the OSCC cancer stem (-like) cell (CSC) signature. Notably, suppression of CDK5RAP2 expression disrupts spindle orientation during mitosis. Collectively, these results identify CDK5RAP2 as a potential CSC marker and reveal a mechanism that controls the CSC population in OSCC.

Publication types

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

MeSH terms

Cell Cycle Proteins* / genetics
Cell Cycle Proteins* / metabolism
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Gene Expression Regulation, Neoplastic
Humans
Mouth Neoplasms* / genetics
Nerve Tissue Proteins* / genetics
Nerve Tissue Proteins* / metabolism
Squamous Cell Carcinoma of Head and Neck* / genetics

Substances

CDK5RAP2 protein, human
Cell Cycle Proteins
Nerve Tissue Proteins