Anti‐apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells

Zhang, Xiaomeng; Wang, Qi; Ling, Ming-Tat; Wong, Yong Chuan; Leung, Siu Ling; Wang, Xianghong

doi:10.1002/ijc.22489

Cited by 64 publications

(48 citation statements)

References 31 publications

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“…This phenotypic behavior is associated with extensive genetic reprogramming, most notable through the actions of a family of transcription factors such as Snail, Zeb [31], FOXC2, HMGA and Twist. These factors play critical roles in mesoderm formation during embryonic development and can protect cells from apoptosis in vitro [33,34]. The sensitivity of tumor cells to the EGFR tyrosine kinase inhibitor erlotinib has been reported to correlate with EMT status in multiple cancer lines.…”

Section: Discussionmentioning

confidence: 99%

Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy

Thomson¹,

Petti²,

Sujka-Kwok³

et al. 2008

Clin Exp Metastasis

175

147

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NSCLC cells with a mesenchymal phenotype have shown a marked reduction in sensitivity to EGFR inhibitors, though the molecular rationale has remained obscure. Here we find that in mesenchymal-like tumor cells both tyrosine phosphorylation of EGFR, ErbB2, and ErbB3 signaling networks and expression of EGFR family ligands were decreased. While chronic activation of EGFR can promote an EMT-like transition, once having occurred EGFR family signaling was attenuated. We investigated the mechanisms by which mesenchymal-like cells bypass EGFR signaling and acquire alternative routes of proliferative and survival signaling. Mesenchymal-like NSCLC cells exhibit aberrant PDGFR and FGFR expression and autocrine signaling through these receptors can activate the MEK-ERK and PI3K pathways. Selective pharmacological inhibition of PDGFR or FGFR receptor tyrosine kinases reduced cell proliferation in mesenchymal-like but not epithelial NSCLC cell lines. A metastable, reversible EMT-like transition in the NSCLC line H358 was achieved by exogenous TGFb, which served as a model EMT system. The H358/TGFb cells showed many of the attributes of established mesenchymal-like NSCLC cells including a loss of cell-cell junctions, a loss of EGF-family ligand expression, a loss of ErbB3 expression, increased EGFRindependent Mek-Erk pathway activation and reduced sensitivity to EGFR inhibition. Notably an EMT-dependent acquisition of PDGFR, FGFR and TGFb receptors in H358/TGFbeta cells was also observed. In H358/TGFbeta cells both PDGFR and FGFR showed functional ligand stimulation of their intrinsic tyrosine kinase activities. The findings of kinase switching and acquired PDGFR and FGFR signaling suggest investigation of new inhibitor combinations to target NSCLC metastases.

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Section: Discussionmentioning

confidence: 99%

Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy

Thomson¹,

Petti²,

Sujka-Kwok³

et al. 2008

Clin Exp Metastasis

175

147

View full text Add to dashboard Cite

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“…Recent reports suggest that high levels of Twist-1 confer cancer cells resistance to various chemotherapeutic drugs (Pham et al, 2007;Zhang et al, 2007;Shiota et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Twist-1 transactivates the PKBb promoter and a positive association between elevated levels of Twist-1 and PKBb has been found in late-stage breast cancer samples (Cheng et al, 2007). PKB in turn might behave as a functional mediator of Twist-1 and is involved in Twist-mediated chemotherapeutic drug resistance (Cheng et al, 2007;Zhang et al, 2007). Interestingly, Saethre-Chotzen syndrome resulting from Twist-1 haploinsufficiency displays decreased expression of Cbl ubiquitin ligase, resulting in the accumulation of phosphatidylinositol-3-kinase (PI3K) and increased PI3K/PKB signaling (Guenou et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage

et al. 2010

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Protein kinase B (PKB/Akt) is ubiquitously expressed in cells. Phosphorylation of its multiple targets in response to various stimuli, including growth factors or cytokines, promotes cell survival and inhibits apoptosis. PKB is upregulated in many different cancers and a significant amount of the enzyme is present in its activated form. Here we show that PKB phosphorylates one of the anti-apoptotic proteins-transcription factor Twist-1 at Ser42. Cells expressing Twist-1 displayed inefficient p53 upregulation in response to DNA damage induced by c-irradiation or the genotoxic drug adriamycin. This influenced the activation of p53 target genes such as p21 Waf1 and Bax and led to aberrant cell-cycle regulation and the inhibition of apoptosis. The impaired induction of these p53 effector molecules is likely to be mediated by PKB-dependent phosphorylation of Twist-1 because, unlike the wild-type mutant, the Twist-1 S42A mutant did not confer cell resistance to DNA damage. Moreover, phosphorylation of Twist-1 at Ser42 was shown in vivo in various human cancer tissues, suggesting that this posttranslational modification ensures functional activation of Twist-1 after promotion of survival during carcinogenesis.

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“…32 Enhanced expression of TWIST and ectopic expression of Id-1 have been separately found to protect nasopharyngeal cancer cells from taxol-induced cell death. [33][34][35] Wang et al 36 have reported that silencing of the CK8 gene increased cisplatin toxicity in HONE1 nasopharyngeal cancer cells. Mei et al 37 have observed that there was enhanced chemosensitivity to bleomycin and cisplatin, following siRNA-mediated knockdown of LMP1 in EBV-positive C666-1 cells.…”

Section: Discussionmentioning

confidence: 99%

Y-Box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer

et al. 2009

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The Y-Box-binding protein-1, a member of the cold-shock domain DNA-and RNA-binding protein superfamily, is known to mediate chemoresistance. The aim of this study was to determine the expression of Y-Box- Y-Box-binding protein-1 immunostaining was observed to be predominantly cytoplasmic. A higher recurrence of nasopharyngeal cancer was found in patients whose tissues had increased Y-Box-binding protein-1 expression (Po0.001). The Cox proportionate hazard regression model also established that high Y-Box-binding protein-1 immunoreactivity was significantly correlated with increased risk (2.13 times) of recurrence as compared to low Y-Box-binding protein-1 immunoreactivity (P ¼ 0.01). Within groups of patients treated by radiotherapy or chemoradiotherapy, recurrent cases had significantly higher Y-Box-binding protein-1 expression than nonrecurrent cases (Po0.001 and P ¼ 0.0035, respectively). These data suggest that Y-Box-binding protein-1 expression has clinicopathological significance with potential as a predictive marker of recurrence in nasopharyngeal cancer patients who undergo radiotherapy or chemoradiotherapy.

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Anti‐apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells

Cited by 64 publications

References 31 publications

Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy

Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy

PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage

Y-Box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer

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