Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan;52(1):47-55.
doi: 10.1111/jop.13382. Epub 2022 Nov 22.

TOMM34 promotes cell proliferation, migration, and invasion of OSCC and modulates mitochondrial function

Yunyi Huang  1 , Zhipei Chen  1 , Xuanyi Chen  1 , Xiaohua Chen  1 , Meng Xu  1
Affiliations

TOMM34 promotes cell proliferation, migration, and invasion of OSCC and modulates mitochondrial function

Yunyi Huang et al. J Oral Pathol Med. 2023 Jan.

Abstract

Background: 34-kDa translocase of the outer mitochondrial membrane (TOMM34) has been reported highly expressed in many cancers and is positively correlated to poorer prognosis. Our prior study showed TOMM34 is highly expressed in oral squamous cell carcinoma (OSCC) and is closely related to TNM classification and tumor size. TOMM34 is also associated with lymph node metastasis and poorer overall survival and disease-free survival in HPV-negative OSCC.

Methods: We knocked down TOMM34 in OSCC cells (SCC15, HPV positive; Cal27, HPV negative) with siRNA and over-expressed with plasmids. The effects of TOMM34 on cell proliferation, migration and invasion abilities were detected by EdU assay, CCK-8 assay, wound-healing assay, and Transwell assay. We also detected the mitochondrial morphology and the intracellular Reactive Oxygen Species (ROS) level by fluorescence staining and flow cytometry. Finally, we monitored the protein levels of ERK pathway-related molecules.

Results: TOMM34 knockdown decreased the proliferation in SCC15 and Cal27, and weakened the migration and invasion abilities as well. Mitochondria became shorter, in the shape of dots or short rods, suggesting that mitochondrial damage occurred. Intracellular ROS levels increased significantly after knockdown TOMM34 and decreased after over-expressing TOMM34. The phosphorylation levels of ERK1/2 and MEK1/2 in SCC15 were significantly higher than in Cal27. Besides, the phosphorylation levels of ERK1/2 and MEK1/2 were inhibited in SCC15 after knockdown of TOMM34, but not in Cal27.

Conclusion: TOMM34 promotes the cell proliferation, migration, and invasion of OSCC. In addition, TOMM34 participates in maintaining the mitochondrial shape and reducing the intracellular ROS level to protect cancer cells. Furthermore, TOMM34 increases the activity of ERK1/2 and MEK1/2 in HPV-positive OSCC cells but not in HPV-negative.

Keywords: HPV; OSCC; ROS; TOMM34; mitochondria.

PubMed Disclaimer

References

REFERENCE

    1. Hübbers CU, Akgül B. HPV and cancer of the oral cavity. Virulence. 2015;6(3):244-248.
    1. Li H, Torabi SJ, Yarbrough WG, Mehra S, Osborn HA, Judson B. Association of Human Papillomavirus Status at head and neck carcinoma subsites with overall survival. JAMA Otolaryngol Head Neck Surg. 2018;144(6):519-525.
    1. Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer. 2005;114(5):806-816.
    1. Sorroche BP, Talukdar FR, Lima SCS, et al. DNA methylation markers from negative surgical margins can predict recurrence of Oral squamous cell carcinoma. Cancers (Basel). 2021;13(12):2915.
    1. Zong WX, Rabinowitz JD, White E. Mitochondria and cancer. Mol Cell. 2016;61(5):667-676.

MeSH terms

Substances

LinkOut - more resources