Disease relevance of Anoikis

• The neurotrophic receptor TrkB in anoikis resistance and metastasis: a perspective [1].
• We conclude that the S100A7-Jab1 pathway acts to enhance survival under conditions of cellular stress, such as anoikis, which may promote progression of breast cancer [2].
• Tyrosine kinase-dependent, phosphatidylinositol 3'-kinase, and mitogen-activated protein kinase-independent signaling pathways prevent lung adenocarcinoma cells from anoikis [3].
• Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B [4].
• CD99-forced expression in two osteosarcoma cell lines significantly reduced resistance to anoikis, inhibited growth in anchorage independence as well as cell migration, and led to abrogation of tumorigenic and metastatic ability [5].

High impact information on Anoikis

• Increasing Bit1 expression enhances anoikis, while suppressing the expression reduces it [6].
• Loss of cell attachment to the ECM causes apoptosis, a process known as anoikis [6].
• Certain cell types undergo apoptosis when they lose integrin-mediated contacts with the extracellular matrix ("anoikis") [7].
• Certain damage signals, such as loss of cell attachment (anoikis), unleash Bmf, allowing it to translocate and bind prosurvival Bcl-2 proteins [8].
• Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis [8].

Chemical compound and disease context of Anoikis

• Indeed, our results open the possibility to develop new celecoxib derivatives that induce anoikis without COX-2 inhibition so as to avoid the cardiovascular toxicity recently described for the COX-2 inhibitors [9].
• In bcl-2 over expressing prostate cancer cells there was significant suppression of doxazosin induced anoikis and cell invasion compared with neocontrol transfectants (p <0.05) [10].
• CONCLUSIONS: These findings demonstrate that the quinazoline derived alpha1-antagonists doxazosin and terazosin but not sulfonamide based tamsulosin induce anoikis and inhibit prostate cancer cell invasion, an effect that is antagonized by bcl-2 [10].
• Alpha 4 integrin increases anoikis of human osteosarcoma cells [11].
• The quinazoline-derived alpha1-adrenoceptor antagonists, doxazosin and terazosin have been recently shown to induce an anoikis effect in human prostate cancer cells and to suppress prostate tumor vascularity in clinical specimens [Keledjian and Kyprianou, 2003] [12].

Biological context of Anoikis

• The central problem of anoikis is to understand how integrin-mediated cell adhesion signals control the apoptotic machinery [13].
• Bim is strongly induced after cell detachment and downregulation of Bim expression by RNA interference (RNAi) inhibits anoikis [14].
• CONCLUSIONS: Distinct p38 isoforms play a major role in the induction of enterocytic anoikis and the regulation of such selective p38 isoform-mediated anoikis is linked with the state of cell differentiation [15].
• Adenovirus-mediated transfection of caspase-8 augments anoikis and inhibits peritoneal dissemination of human gastric carcinoma cells [16].
• Pgrn stimulates the invasion of SW-13 cells across Matrigel-coated filters, increases the expression of matrix metalloproteinase 13 and 17, protects against anoikis, and overcomes the inhibition of cell growth imposed on SW-13 cells by interstitial type-I collagen [17].

Anatomical context of Anoikis

• The resulting higher Akt1 activity leads to increased keratinocyte survival following growth factor deprivation or anoikis [18].
• Differentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikis [15].
• Matrix attachment regulates Fas-induced apoptosis in endothelial cells: a role for c-flip and implications for anoikis [19].
• Moreover, concomitant activation of p53 and inhibition of Akt are both necessary and sufficient to signal anoikis in primary fibroblasts [20].
• Small interfering RNA-mediated down-regulation of NR4A2 in HeLa cells, either transiently or stably, resulted in reduced anchorage-independent growth that was largely attributable to increased anoikis [21].

Associations of Anoikis with chemical compounds

• Another early response to cell suspension was the activation of the ICE-related cysteine protease, ICE/LAP3; this activation and anoikis were suppressed by the ICE-protease inhibitor, crmA [22].
• The insulin-like growth factor I receptor is required for Akt activation and suppression of anoikis in cells transformed by the ETV6-NTRK3 chimeric tyrosine kinase [23].
• Unexpectedly, oncogenic Ras failed to activate Akt, and treatment of Ras-transformed RIE-1 cells with the LY294002 PI3K inhibitor did not affect anoikis resistance or growth in soft agar [24].
• Here we demonstrate that G(1)/S arrest by overexpression of the cyclin-dependent kinase inhibitors p16(INK4a), p21(Cip1), or p27(Kip1) or by treatment with mimosine or aphidicolin confers anoikis resistance in MCF-10A cells [25].
• Tyrosine kinase inhibitor genistein rendered three of them sensitive to anoikis [3].

Gene context of Anoikis

• Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis [14].
• Resistance to anoikis correlated with PKB/Akt activation in suspension, but not with changes in PTEN or p110alpha PI3 kinase levels [26].
• Surprisingly, we found that ERK and phosphatidylinositol 3'-kinase/AKT activation did not have significant roles in conferring anoikis resistance [27].
• Human carcinoembryonic antigen functions as a general inhibitor of anoikis [28].
• The IGF-I signal recovered by MMP-7 protected against apoptosis induced by anoikis in 3T3-IGF-IR cells [29].

Analytical, diagnostic and therapeutic context of Anoikis

• Using gene silencing and gene transfer techniques, we show that increased expression of the apoptosis inhibitory protein XIAP contributes to anoikis resistance of the circulating metastatic human prostate carcinoma cells [30].
• Western blot analysis demonstrated that neither p53 nor Bcl-2, Bcl-XL and Bax protein expression changed during anoikis [31].
• The signaling events culminating in anoikis are still unclear; recent studies have implicated Stress Activated Protein Kinase (SAPK), also known as Jun-N-Terminal kinase, as a potentially crucial signal transducer and mediator of anoikis [32].
• Expression of KLF5 in TE2 cells inhibits proliferation, and both KLF4 and KLF5 decrease viability after treatment with hydrogen peroxide and increase anoikis [33].

References