TY - JOUR
T1 - Modulated Start-Up Mode of Cancer Cell Migration Through Spinophilin-Tubular Networks
AU - Hwang, Soyoung
AU - Lee, Peter Chang Whan
AU - Shin, Dong Min
AU - Hong, Jeong Hee
N1 - Publisher Copyright:
© Copyright © 2021 Hwang, Lee, Shin and Hong.
PY - 2021/3/9
Y1 - 2021/3/9
N2 - 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.
AB - 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.
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U2 - 10.3389/fcell.2021.652791
DO - 10.3389/fcell.2021.652791
M3 - Article
AN - SCOPUS:85102931179
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
SN - 2296-634X
M1 - 652791
ER -