Survie cellulaire : differences et différenciation

Vachon, Pierre H.

doi:10.1051/medsci/2006224423

Cited by 10 publications

(63 citation statements)

References 33 publications

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“…Consequently, incoming extracellular signals determine in large part if a cell lives or dies through signaling events that affect the expression and/or functions of multiple antiand pro-apoptotic Bcl-2 homologs [2][3][4][5][6][7][8]. Such signals are provided by various cues, including cell adhesion.…”

Section: Introductionmentioning

confidence: 99%

“…Such signals are provided by various cues, including cell adhesion. To this effect, the disruption, or loss, of integrin-mediated cell adhesion induces apoptosis by a process that is termed anoikis [4][5][6][7][8]. In epithelial cells, those integrins belonging to the b1 subfamily are not only largely responsible for the establishment of a physical link between the extracellular matrix (ECM) and the cytoskeleton, but as well for the cell adhesion-mediated activation of signaling pathways [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…To this effect, the disruption, or loss, of integrin-mediated cell adhesion induces apoptosis by a process that is termed anoikis [4][5][6][7][8]. In epithelial cells, those integrins belonging to the b1 subfamily are not only largely responsible for the establishment of a physical link between the extracellular matrix (ECM) and the cytoskeleton, but as well for the cell adhesion-mediated activation of signaling pathways [5][6][7][8][9][10]. Hence, signaling originating from b1 integrins to promote cell survival often implicate Fak (p125 Fak ), Src (p60 Src ), the MEK-1, -2/Erk-1, -2 (p42 Erk2 /p44 Erk1 MAPK) pathway and/ or the PI3-K/Akt (p57 Akt ) pathway, depending on the tissue and cellular context [5][6][7][8][9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…In epithelial cells, those integrins belonging to the b1 subfamily are not only largely responsible for the establishment of a physical link between the extracellular matrix (ECM) and the cytoskeleton, but as well for the cell adhesion-mediated activation of signaling pathways [5][6][7][8][9][10]. Hence, signaling originating from b1 integrins to promote cell survival often implicate Fak (p125 Fak ), Src (p60 Src ), the MEK-1, -2/Erk-1, -2 (p42 Erk2 /p44 Erk1 MAPK) pathway and/ or the PI3-K/Akt (p57 Akt ) pathway, depending on the tissue and cellular context [5][6][7][8][9][10][11][12][13][14][15][16][17]. It is well established that integrin/Fak/Src signaling can stimulate the PI3-K/Akt and MEK/Erk pathways, either individually or in combination, depending on the cell type analyzed [5][6][7][8][9][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…Hence, signaling originating from b1 integrins to promote cell survival often implicate Fak (p125 Fak ), Src (p60 Src ), the MEK-1, -2/Erk-1, -2 (p42 Erk2 /p44 Erk1 MAPK) pathway and/ or the PI3-K/Akt (p57 Akt ) pathway, depending on the tissue and cellular context [5][6][7][8][9][10][11][12][13][14][15][16][17]. It is well established that integrin/Fak/Src signaling can stimulate the PI3-K/Akt and MEK/Erk pathways, either individually or in combination, depending on the cell type analyzed [5][6][7][8][9][14][15][16][17]. In this respect, MEK/Erk and PI3-K/Akt are known for their implication in the regulation of the expression of Bcl-2 homologs, as well as the inhibitory phosphorylation of Bad on its serine112 and/or serine136 residues [3, 6-8, 11-14, 18].…”

Section: Introductionmentioning

confidence: 99%

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β1 integrin/Fak/Src signaling in intestinal epithelial crypt cell survival: integration of complex regulatory mechanisms

et al. 2008

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The molecular determinants which dictate survival and apoptosis/anoikis in human intestinal crypt cells remain to be fully understood. To this effect, the roles of beta1 integrin/Fak/Src signaling to the PI3-K/Akt-1, MEK/Erk, and p38 pathways, were investigated. The regulation of six Bcl-2 homologs (Bcl-2, Mcl-1, Bcl-X(L), Bax, Bak, Bad) was likewise analyzed. We report that: (1) Anoikis causes a down-activation of Fak, Src, Akt-1 and Erk1/2, a loss of Fak-Src association, and a sustained/enhanced activation of p38beta, which is required as apoptosis/anoikis driver; (2) PI3-K/Akt-1 up-regulates the expression of Bcl-X(L) and Mcl-1, down-regulates Bax and Bak, drives Bad phosphorylation (both serine112/136 residues) and antagonizes p38beta activation; (3) MEK/Erk up-regulates Bcl-2, drives Bad phosphorylation (serine112 residue), but does not antagonize p38bactivation; (4) PI3-K/Akt-1 is required for survival, whereas MEK/Erk is not; (5) Src acts as a cornerstone in the engagement of both pathways by beta1 integrins/Fak, and is crucial for survival; and (6) beta1 integrins/Fak and/or Src regulate Bcl-2 homologs as both PI3-K/Atk-1 and MEK/Erk combined. Hence, beta1 integrin/Fak/Src signaling translates into integrated mediating functions of p38beta activation and regulation of Bcl-2 homologs by PI3-K/Akt-1 and MEK/Erk, consequently determining their requirement (or not) for survival.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

β1 integrin/Fak/Src signaling in intestinal epithelial crypt cell survival: integration of complex regulatory mechanisms

et al. 2008

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Anoikis Regulation: Complexities, Distinctions, and Cell Differentiation

Beauséjour

Boutin

Vachon

2018

Apoptosis and Beyond

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Intestinal epithelial cancer cell anoikis resistance: EGFR‐mediated sustained activation of Src overrides Fak‐dependent signaling to MEK/Erk and/or PI3‐K/Akt‐1

Demers

Thibodeau

Noël

et al. 2009

J of Cellular Biochemistry

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Herein, we investigated the survival roles of Fak, Src, MEK/Erk, and PI3-K/Akt-1 in intestinal epithelial cancer cells (HCT116, HT29, and T84), in comparison to undifferentiated and differentiated intestinal epithelial cells (IECs). We report that: (1) cancer cells display striking anoikis resistance, as opposed to undifferentiated/differentiated IECs; (2) under anoikis conditions and consequent Fak down-activation, cancer cells nevertheless exhibit sustained Fak-Src interactions and Src/MEK/Erk activation, unlike undifferentiated/differentiated IECs; however, HCT116 and HT29 cells exhibit a PI3-K/Akt-1 down-activation, as undifferentiated/differentiated IECs, whereas T84 cells do not; (3) cancer cells require MEK/Erk for survival, as differentiated (but not undifferentiated) IECs; however, T84 cells do not require Fak and HCT116 cells do not require PI3-K/Akt-1, in contrast to the other cells studied; (4) Src acts as a cornerstone in Fak-mediated signaling to MEK/Erk and PI3-K/Akt-1 in T84 cells, as in undifferentiated IECs, whereas PI3-K/Akt-1 is Src-independent in HCT116, HT29 cells, as in differentiated IECs; and (5) EGFR activity inhibition abrogates anoikis resistance in cancer cells through a loss of Fak-Src interactions and down-activation of Src/MEK/Erk (T84, HCT116, HT29 cells) and PI3-K/Akt-1 (T84 cells). Hence, despite distinctions in signaling behavior not necessarily related to undifferentiated or differentiated IECs, intestinal epithelial cancer cells commonly display an EGFR-mediated sustained activation of Src under anoikis conditions. Furthermore, such sustained Src activation confers anoikis resistance at least in part through a consequent sustenance of Fak-Src interactions and MEK/Erk activation, thus not only overriding Fak-mediated signaling to MEK/Erk and/or PI3-K/Akt-1, but also the requirement of Fak and/or PI3-K/Akt-1 for survival.

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Survie cellulaire : differences et différenciation

Cited by 10 publications

References 33 publications

β1 integrin/Fak/Src signaling in intestinal epithelial crypt cell survival: integration of complex regulatory mechanisms

β1 integrin/Fak/Src signaling in intestinal epithelial crypt cell survival: integration of complex regulatory mechanisms

Anoikis Regulation: Complexities, Distinctions, and Cell Differentiation

Intestinal epithelial cancer cell anoikis resistance: EGFR‐mediated sustained activation of Src overrides Fak‐dependent signaling to MEK/Erk and/or PI3‐K/Akt‐1

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