SFPQ Promotes Lung Cancer Malignancy via Regulation of CD44 v6 Expression

Libang Yang; Jianbo Yang; Blake Jacobson; Adam Gilbertsen; Karen Smith; LeeAnn Higgins; Candace Guerrero; Hong Xia; Craig A Henke; Jizhen Lin

doi:10.3389/fonc.2022.862250

SFPQ Promotes Lung Cancer Malignancy via Regulation of CD44 v6 Expression

Front Oncol. 2022 May 30:12:862250. doi: 10.3389/fonc.2022.862250. eCollection 2022.

Authors

Libang Yang¹, Jianbo Yang^{2

3}, Blake Jacobson⁴, Adam Gilbertsen¹, Karen Smith¹, LeeAnn Higgins⁵, Candace Guerrero⁵, Hong Xia¹, Craig A Henke¹, Jizhen Lin^{3

6}

Affiliations

¹ Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
² Department of Laboratory Medicine and Pathology, School of Medicine, University of Minneapolis, Minneapolis, MN, United States.
³ The Cancer Center, Fujian Medical University Union Hospital, Fuzhou, China.
⁴ Hematology, Oncology and Transplantation, School of Medicine, University of Minnesota, Minneapolis, MN, United States.
⁵ Center for Mass Spectrometry and Proteomics, University of Minnesota, St. Paul, MN, United States.
⁶ The Immunotherapy Research Laboratory, Department of Otolaryngology, Cancer Center, University of Minnesota, Minneapolis, MN, United States.

Abstract

Mesenchymal stem cells (MSCs) contribute to tumor pathogenesis and elicit antitumor immune responses in tumor microenvironments. Nuclear proteins might be the main players in these processes. In the current study, combining spatial proteomics with ingenuity pathway analysis (IPA) in lung non-small cell (NSC) cancer MSCs, we identify a key nuclear protein regulator, SFPQ (Splicing Factor Proline and Glutamine Rich), which is overexpressed in lung cancer MSCs and functions to promote MSCs proliferation, chemical resistance, and invasion. Mechanistically, the knockdown of SFPQ reduces CD44v6 expression to inhibit lung cancer MSCs stemness, proliferation in vitro, and metastasis in vivo. The data indicates that SFPQ may be a potential therapeutic target for limiting growth, chemotherapy resistance, and metastasis of lung cancer.

Keywords: CD44v6; SFPQ; ingenuity pathway analysis; lung non-small cell (NSC) cancer; mesenchymal stem cells (MSCs); nuclear fraction; quantitative proteomics.