Modulated Start-Up Mode of Cancer Cell Migration Through Spinophilin-Tubular Networks

Soyoung Hwang; Peter Chang-Whan Lee; Dong Min Shin; Jeong Hee Hong

doi:10.3389/fcell.2021.652791

Modulated Start-Up Mode of Cancer Cell Migration Through Spinophilin-Tubular Networks

Front Cell Dev Biol. 2021 Mar 9:9:652791. doi: 10.3389/fcell.2021.652791. eCollection 2021.

Authors

Soyoung Hwang¹, Peter Chang-Whan Lee², Dong Min Shin³, Jeong Hee Hong^{1

4}

Affiliations

¹ Department of Physiology, College of Medicine, Gachon University, Incheon, South Korea.
² Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
³ Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.
⁴ Department of Health Sciences and Technology, GAIHST, Lee Gil Ya Cancer and Diabetes Institute, Incheon, South Korea.

Abstract

Spinophilin (SPL) is a multifunctional actin-binding scaffolding protein. Although increased research on SPL in cancer biology has revealed a tumor suppressive role, its modulation in cancer biology, and oncological relevance remains elusive. Thus, we determined the role of SPL in the modulation of the junctional network and cellular migration in A549 lung cancer cell line. Knockdown of SPL promoted cancer cell invasion in agarose spot and scratch wound assays. Attenuation of SPL expression also enhanced invadopodia, as revealed by enhanced vinculin spots, and enhanced sodium bicarbonate cotransporter NBC activity without enhancing membranous expression of NBCn1. Disruption of the tubular structure with nocodazole treatment revealed enhanced SPL expression and reduced NBC activity and A549 migration. SPL-mediated junctional modulation and tubular stability affected bicarbonate transporter activity in A549 cells. The junctional modulatory function of SPL in start-up migration, such as remodeling of tight junctions, enhanced invadopodia, and increased NBC activity, revealed here would support fundamental research and the development of an initial target against lung cancer cell migration.

Keywords: bicarbonate transporter; migration; spinophilin; tight junction; tubular network.