Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells

Research output: Contribution to journalArticle

Standard

Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells. / Bourseau-Guilmain, Erika; Menard, Julien; Lindqvist, E.; Indira Chandran, Vineesh; CHRISTIANSON, HELENA; Cerezo Magana, Myriam; Lidfeldt, Jon; Marko-Varga, György; Welinder, Charlotte; Belting, Mattias.

In: Nature Communications, Vol. 7, 11371, 20.04.2016, p. 1-13.

Research output: Contribution to journalArticle

Harvard

Bourseau-Guilmain, E, Menard, J, Lindqvist, E, Indira Chandran, V, CHRISTIANSON, HELENA, Cerezo Magana, M, Lidfeldt, J, Marko-Varga, G, Welinder, C & Belting, M 2016, 'Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells', Nature Communications, vol. 7, 11371, pp. 1-13. https://doi.org/10.1038/ncomms11371

APA

Bourseau-Guilmain, E., Menard, J., Lindqvist, E., Indira Chandran, V., CHRISTIANSON, HELENA., Cerezo Magana, M., ... Belting, M. (2016). Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells. Nature Communications, 7, 1-13. [11371]. https://doi.org/10.1038/ncomms11371

CBE

MLA

Vancouver

Bourseau-Guilmain E, Menard J, Lindqvist E, Indira Chandran V, CHRISTIANSON HELENA, Cerezo Magana M et al. Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells. Nature Communications. 2016 Apr 20;7:1-13. 11371. https://doi.org/10.1038/ncomms11371

Author

Bourseau-Guilmain, Erika ; Menard, Julien ; Lindqvist, E. ; Indira Chandran, Vineesh ; CHRISTIANSON, HELENA ; Cerezo Magana, Myriam ; Lidfeldt, Jon ; Marko-Varga, György ; Welinder, Charlotte ; Belting, Mattias. / Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells. In: Nature Communications. 2016 ; Vol. 7. pp. 1-13.

RIS

TY - JOUR

T1 - Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells

AU - Bourseau-Guilmain, Erika

AU - Menard, Julien

AU - Lindqvist, E.

AU - Indira Chandran, Vineesh

AU - CHRISTIANSON, HELENA

AU - Cerezo Magana, Myriam

AU - Lidfeldt, Jon

AU - Marko-Varga, György

AU - Welinder, Charlotte

AU - Belting, Mattias

PY - 2016/4/20

Y1 - 2016/4/20

N2 - Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we identify several proteins that can override caveolin-1 negative regulation, exhibiting increased internalization at hypoxia. We demonstrate antibody-mediated cytotoxin delivery and killing specifically of hypoxic cells through one of these proteins, carbonic anhydrase IX. Our data reveal that caveolin-1 modulates cell-surface proteome turnover at hypoxia with potential implications for specific targeting of the hypoxic tumour microenvironment.

AB - Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we identify several proteins that can override caveolin-1 negative regulation, exhibiting increased internalization at hypoxia. We demonstrate antibody-mediated cytotoxin delivery and killing specifically of hypoxic cells through one of these proteins, carbonic anhydrase IX. Our data reveal that caveolin-1 modulates cell-surface proteome turnover at hypoxia with potential implications for specific targeting of the hypoxic tumour microenvironment.

KW - Hypoxia

KW - cancer cells

UR - http://www.scopus.com/inward/record.url?scp=84964863959&partnerID=8YFLogxK

U2 - 10.1038/ncomms11371

DO - 10.1038/ncomms11371

M3 - Article

VL - 7

SP - 1

EP - 13

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 11371

ER -