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Decreased camptothecin sensitivity of the stem-cell-like fraction of caco2 cells correlates with an altered phosphorylation pattern of topoisomerase I

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Decreased camptothecin sensitivity of the stem-cell-like fraction of caco2 cells correlates with an altered phosphorylation pattern of topoisomerase I. / Roy, Amit; Tesauro, Cinzia; Frøhlich, Rikke; Hede, Marianne S; Nielsen, Maria J; Kjeldsen, Eigil; Bonven, Bjarne; Stougaard, Magnus; Gromova, Irina; Knudsen, Birgitta R.

In: PLOS ONE, Vol. 9, No. 6, e99628, 2014.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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@article{b6d3663c23614a0c93b61a7c2aa33651,
title = "Decreased camptothecin sensitivity of the stem-cell-like fraction of caco2 cells correlates with an altered phosphorylation pattern of topoisomerase I",
abstract = "The CD44+ and CD44- subpopulations of the colorectal cancer cell line Caco2 were analyzed separately for their sensitivities to the antitumor drug camptothecin. CD44+ cells were less sensitive to camptothecin than CD44- cells. The relative resistance of CD44+ cells was correlated with (i) reduced activity of the nuclear enzyme topoisomerase I and (ii) insensitivity of this enzyme to camptothecin when analyzed in extracts. In contrast, topoisomerase I activity was higher in extracts from CD44- cells and the enzyme was camptothecin sensitive. Topoisomerase I from the two subpopulations were differentially phosphorylated in a manner that appeared to determine the drug sensitivity and activity of the enzyme. This finding was further supported by the fact that phosphorylation of topoisomerase I in CD44+ cell extract by protein kinase CK2 converted the enzyme to a camptothecin sensitive, more active form mimicking topoisomerase I in extracts from CD44- cells. Conversely, dephosphorylation of topoisomerase I in extracts from CD44- cells rendered the enzyme less active and camptothecin resistant. These findings add to our understanding of chemotherapy resistance in the Caco2 CD44+ cancer stem cell model.",
author = "Amit Roy and Cinzia Tesauro and Rikke Fr{\o}hlich and Hede, {Marianne S} and Nielsen, {Maria J} and Eigil Kjeldsen and Bjarne Bonven and Magnus Stougaard and Irina Gromova and Knudsen, {Birgitta R}",
year = "2014",
doi = "10.1371/journal.pone.0099628",
language = "English",
volume = "9",
journal = "P L o S One",
issn = "1932-6203",
publisher = "public library of science",
number = "6",

}

RIS

TY - JOUR

T1 - Decreased camptothecin sensitivity of the stem-cell-like fraction of caco2 cells correlates with an altered phosphorylation pattern of topoisomerase I

AU - Roy, Amit

AU - Tesauro, Cinzia

AU - Frøhlich, Rikke

AU - Hede, Marianne S

AU - Nielsen, Maria J

AU - Kjeldsen, Eigil

AU - Bonven, Bjarne

AU - Stougaard, Magnus

AU - Gromova, Irina

AU - Knudsen, Birgitta R

PY - 2014

Y1 - 2014

N2 - The CD44+ and CD44- subpopulations of the colorectal cancer cell line Caco2 were analyzed separately for their sensitivities to the antitumor drug camptothecin. CD44+ cells were less sensitive to camptothecin than CD44- cells. The relative resistance of CD44+ cells was correlated with (i) reduced activity of the nuclear enzyme topoisomerase I and (ii) insensitivity of this enzyme to camptothecin when analyzed in extracts. In contrast, topoisomerase I activity was higher in extracts from CD44- cells and the enzyme was camptothecin sensitive. Topoisomerase I from the two subpopulations were differentially phosphorylated in a manner that appeared to determine the drug sensitivity and activity of the enzyme. This finding was further supported by the fact that phosphorylation of topoisomerase I in CD44+ cell extract by protein kinase CK2 converted the enzyme to a camptothecin sensitive, more active form mimicking topoisomerase I in extracts from CD44- cells. Conversely, dephosphorylation of topoisomerase I in extracts from CD44- cells rendered the enzyme less active and camptothecin resistant. These findings add to our understanding of chemotherapy resistance in the Caco2 CD44+ cancer stem cell model.

AB - The CD44+ and CD44- subpopulations of the colorectal cancer cell line Caco2 were analyzed separately for their sensitivities to the antitumor drug camptothecin. CD44+ cells were less sensitive to camptothecin than CD44- cells. The relative resistance of CD44+ cells was correlated with (i) reduced activity of the nuclear enzyme topoisomerase I and (ii) insensitivity of this enzyme to camptothecin when analyzed in extracts. In contrast, topoisomerase I activity was higher in extracts from CD44- cells and the enzyme was camptothecin sensitive. Topoisomerase I from the two subpopulations were differentially phosphorylated in a manner that appeared to determine the drug sensitivity and activity of the enzyme. This finding was further supported by the fact that phosphorylation of topoisomerase I in CD44+ cell extract by protein kinase CK2 converted the enzyme to a camptothecin sensitive, more active form mimicking topoisomerase I in extracts from CD44- cells. Conversely, dephosphorylation of topoisomerase I in extracts from CD44- cells rendered the enzyme less active and camptothecin resistant. These findings add to our understanding of chemotherapy resistance in the Caco2 CD44+ cancer stem cell model.

U2 - 10.1371/journal.pone.0099628

DO - 10.1371/journal.pone.0099628

M3 - Journal article

VL - 9

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 6

M1 - e99628

ER -