TY - JOUR
T1 - FYCO1 regulates accumulation of post-mitotic midbodies by mediating LC3-dependent midbody degradation
AU - Dionne, Lai Kuan
AU - Peterman, Eric
AU - Schiel, John
AU - Gibieža, Paulius
AU - Skeberdis, Vytenis Arvydas
AU - Jimeno, Antonio
AU - Wang, Xiao Jing
AU - Prekeris, Rytis
N1 - Funding Information:
This work was supported in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK064380 to R.P.), Cancer League of Colorado foundation (Research Grant to R.P., X.-J.W.), the National Institutes of Health (DE15953 to X.-J.W. and DE24371 to X.-J.W. and A.J., R01CA149456 to A.J.), and Lietuvos Mokslo Taryba (APP7/2016 to V.A.S.). L.K.D. is supported by a National Cancer Institute T32 training grant (CA174648) and a research grant from Cancer League of Colorado Foundation. P.G. is supported by a WFS National Scholarship program. Deposited in PMC for release after 12 months.
Publisher Copyright:
© 2017.
PY - 2017
Y1 - 2017
N2 - The post-mitotic midbody (MB) is a remnant of cytokinesis that can be asymmetrically inherited by one of the daughter cells following cytokinesis. Until recently, the MB was thought to be degraded immediately following cytokinesis. However, recent evidence suggests that the MB is a protein-rich organelle that accumulates in stem cell and cancer cell populations, indicating that itmay have postmitotic functions. Here, we investigate the role of FYCO1, an LC3- binding protein (herein, LC3 refers to MAP1LC3B), and its function in regulating the degradation of post-mitotic MBs. We show that FYCO1 is responsible for formation of LC3-containing membrane around the post-mitotic MB and that FYCO1 knockdown increases MB accumulation. Although MBs accumulate in the stem-cell-like population of squamous cell carcinomas, FYCO1 depletion does not affect the clonogenicity of these cells. Instead, MB accumulation leads to an increase in anchorage-independent growth and invadopodia formation in HeLa cells and squamous carcinoma cells. Collectively, our data suggest that FYCO1 regulates MB degradation, and we present the first evidence that cancer invasiveness is a feature that can be modulated by the accumulation of MBs in cancer stem cells.
AB - The post-mitotic midbody (MB) is a remnant of cytokinesis that can be asymmetrically inherited by one of the daughter cells following cytokinesis. Until recently, the MB was thought to be degraded immediately following cytokinesis. However, recent evidence suggests that the MB is a protein-rich organelle that accumulates in stem cell and cancer cell populations, indicating that itmay have postmitotic functions. Here, we investigate the role of FYCO1, an LC3- binding protein (herein, LC3 refers to MAP1LC3B), and its function in regulating the degradation of post-mitotic MBs. We show that FYCO1 is responsible for formation of LC3-containing membrane around the post-mitotic MB and that FYCO1 knockdown increases MB accumulation. Although MBs accumulate in the stem-cell-like population of squamous cell carcinomas, FYCO1 depletion does not affect the clonogenicity of these cells. Instead, MB accumulation leads to an increase in anchorage-independent growth and invadopodia formation in HeLa cells and squamous carcinoma cells. Collectively, our data suggest that FYCO1 regulates MB degradation, and we present the first evidence that cancer invasiveness is a feature that can be modulated by the accumulation of MBs in cancer stem cells.
KW - Autophagy
KW - Cytokinesis
KW - Midbody
KW - Post-mitotic accumulation
KW - Post-mitotic degradation
UR - http://www.scopus.com/inward/record.url?scp=85036592963&partnerID=8YFLogxK
U2 - 10.1242/jcs.208983
DO - 10.1242/jcs.208983
M3 - Article
C2 - 29196475
AN - SCOPUS:85036592963
SN - 0021-9533
VL - 130
SP - 4051
EP - 4062
JO - Journal of cell science
JF - Journal of cell science
IS - 23
ER -