A NOVEL PRO-OXIDANT ROLE OF GELSOLIN IN CANCER CELL INVASION
type: CreativeWork
description: Although gelsolin is often implicated in cancer cell invasion, the mechanisms remain poorly understood. We have identified a new role of gelsolin in creating a pro-oxidant milieu thereby enhancing cancer cell invasion. Increased gelsolin expression in HCT116 results in heightened ROS levels, particularly the superoxides (O2-) as well as increased invasion; whereas silencing of gelsolin reduces O2- levels and invasion. Inhbition of O2- produciton using diphenyleneiodonium significanlty attenuates invasion in gelsolin-overexpresing HCT116 cells. Consistently, the invasive capacities of gelsolin-deficient cells were rescued by increasing the O2- levels in these cells. Furthermore we show that gelsolin overexpression suppresses the activity of the antioxidant Cu/Zn SOD, possibly by binding to it. The impairment of Cu/Zn SOD activity provides a mechanistic explanation for the elevated amount of intracellular O2- in gelsolin-overexpressing cells. Therefore, our findings demonstrate a new insight into the role of gelsolin in cancer cell invasion through upregulation of O2- levels.
abstract: Although gelsolin is often implicated in cancer cell invasion, the mechanisms remain poorly understood. We have identified a new role of gelsolin in creating a pro-oxidant milieu thereby enhancing cancer cell invasion. Increased gelsolin expression in HCT116 results in heightened ROS levels, particularly the superoxides (O2-) as well as increased invasion; whereas silencing of gelsolin reduces O2- levels and invasion. Inhbition of O2- produciton using diphenyleneiodonium significanlty attenuates invasion in gelsolin-overexpresing HCT116 cells. Consistently, the invasive capacities of gelsolin-deficient cells were rescued by increasing the O2- levels in these cells. Furthermore we show that gelsolin overexpression suppresses the activity of the antioxidant Cu/Zn SOD, possibly by binding to it. The impairment of Cu/Zn SOD activity provides a mechanistic explanation for the elevated amount of intracellular O2- in gelsolin-overexpressing cells. Therefore, our findings demonstrate a new insight into the role of gelsolin in cancer cell invasion through upregulation of O2- levels.
author: LALCHHANDAMI TOCHHAWNG
keywords: gelsolin, actin, superoxide dismutase, ROS, cancer, invasion,
date published: 2013-01-10
date modified: 2026-07-24T03:33:34Z
provider: National University of Singapore
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: National University of Singapore