MTSS1 is downregulated in nasopharyngeal carcinoma (NPC) which disrupts adherens junctions leading to enhanced cell migration and invasion

Shixing Zheng; Xiaoxia Wang; Liudmila Matskova; Xiaoying Zhou; Zhe Zhang; Elena Kashuba; Ingemar Ernberg; Pontus Aspenström

doi:10.3389/fcell.2023.1275668

MTSS1 is downregulated in nasopharyngeal carcinoma (NPC) which disrupts adherens junctions leading to enhanced cell migration and invasion

Front Cell Dev Biol. 2023 Oct 18:11:1275668. doi: 10.3389/fcell.2023.1275668. eCollection 2023.

Authors

Shixing Zheng^{1

2}, Xiaoxia Wang¹, Liudmila Matskova¹, Xiaoying Zhou³, Zhe Zhang⁴, Elena Kashuba^{1

5}, Ingemar Ernberg¹, Pontus Aspenström^{1

6}

Affiliations

¹ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
² ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.
³ Scientific Research Centre, Life Science Institute, Guangxi Medical University, Nanning, China.
⁴ Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁵ RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, Kyiv, Ukraine.
⁶ Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Abstract

Loss of cell-cell adhesions is the indispensable first step for cancer cells to depart from the primary tumor mass to metastasize. Metastasis suppressor 1 (MTSS1) is frequently lost in metastatic tissues, correlating to advanced tumor stages and poor prognosis across a variety of cancers. Here we explore the anti-metastatic mechanisms of MTSS1, which have not been well understood. We found that MTSS1 is downregulated in NPC tissues. Lower levels of MTSS1 expression correlate to worse prognosis. We show that MTSS1 suppresses NPC cell migration and invasion in vitro through cytoskeletal remodeling at cell-cell borders and assembly of E-cadherin/β-catenin/F-actin in adherens junctions. The I-BAR domain of MTSS1 was both necessary and sufficient to restore this formation of E-cadherin/β-catenin/F-actin-mediated cell adherens junctions.

Keywords: I-BAR domain; MTSS1; adherens junctions; invasion; metastasis; nasopharyngeal carcinoma.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. SZ was a recipient of a Fellowship from the Chinese Scholarship Council (201600160064). XW is a recipient of a Fellowship from the Maternal and Child Health Hospital of Guangxi. This research was supported by Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet), and the National Natural Science Foundation of China Grant No. 81772882 (ZZ) and Grant No. 81960490 (Guangwu Huang). The Figure in the graphical abstract was created with BioRender.