TRAIL-activated EGFR by Cbl-b-regulated EGFR redistribution in lipid rafts antagonises TRAIL-induced apoptosis in gastric cancer cells

Xu, Ling; Zhang, Ye; Liu, Jing; Qu, Junle; Hu, Xuejun; Zhang, Fan; Zheng, Haixue; Qu, Xiujuan; Liu, Yunpeng

doi:10.1016/j.ejca.2012.03.005

Cited by 46 publications

(56 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5A). Our previous study showed that Cbl family proteins regulated TRAIL sensitivity by their translocation into the DISC (Xu et al ., 2012, 2013a,b). Interestingly, our present data showed that DR5 immunoprecipitated with Cbl‐b and c‐Cbl, and these interactions were not changed by TRAIL (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, in the present study, no interaction between DR5 and TRAF2 was detected in gastric cancer cells regardless of TRAIL treatment. Our previous study showed that TRAIL promoted the translocation of Cbl family proteins into the DISC and prevented TRAIL‐triggered apoptosis (Xu et al ., 2012, 2013a,b). However, whether Cbl‐b and c‐Cbl were vital factors in regulating TRAF2‐mediated polyubiquitination of caspase‐8 was unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Isolation of lipid rafts was performed as previously described (Xu et al ., 2012). The gastric cancer cells were incubated with 100 ng·mL −1 TRAIL for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, our earlier work showed the involvement of the E3 ubiquitin ligase casitas B‐lineage lymphoma‐b (Cbl‐b) and its homologue c‐Cbl in TRAIL‐triggered gastric cancer cell apoptosis (Xu et al ., 2009, 2012). Given that c‐Cbl is required for EGF‐induced K48‐linked polyubiquitination of ERBB4 cytoplasmic isoforms (Meijer et al ., 2013), we therefore investigated whether Cbl‐b and c‐Cbl were components of a complex that regulates caspase‐8 polyubiquitination and hence influence the sensitivity of gastric cancer cells to TRAIL.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibits TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells

Zhang

et al. 2017

Molecular Oncology

Self Cite

View full text Add to dashboard Cite

Ubiquitination of caspase‐8 regulates TNF‐related apoptosis‐inducing ligand (TRAIL) sensitivity in cancer cells, and the preligand assembly complex plays a role in caspase‐8 polyubiquitination. However, whether such a complex exists in gastric cancer cells and its role in TRAIL‐triggered apoptosis is unclear. In this study, DR5, casitas B‐lineage lymphoma‐b (Cbl‐b)/c‐Cbl, and TRAF2 formed a complex in TRAIL‐resistant gastric cancer cells, and Cbl‐b and c‐Cbl were the critical adaptors linking DR5 and TRAF2. Treatment with TRAIL induced caspase‐8 translocation into the DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex to interact with TRAF2, which then mediated the K48‐linked polyubiquitination of caspase‐8. The proteasome inhibitor bortezomib markedly enriched the p43/41 products of caspase‐8 activated by TRAIL, indicating proteasomal degradation of caspase‐8. Moreover, TRAF2 knockdown prevented the polyubiquitination of caspase‐8 and thus increased TRAIL sensitivity. In addition, the inhibition of Cbl‐b or c‐Cbl expression and overexpression of miR‐141 targeting Cbl‐b and c‐Cbl partially reversed TRAIL resistance by inhibiting the interaction between TRAF2 and caspase‐8 and the subsequent polyubiquitination of caspase‐8. These results indicate that the DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibited TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Isolation of lipid rafts was performed as previously described (Xu et al ., 2012). The gastric cancer cells were incubated with 100 ng·mL −1 TRAIL for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibits TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells

Zhang

et al. 2017

Molecular Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Subsequently, immunoprecipitates were washed four times with lysis buffer. Immunoprecipitation was performed as described in a previous study (16).…”

Section: Western Blot Analysis the Cells (2x10mentioning

confidence: 99%

Cbl-b promotes cell detachment via ubiquitination of focal adhesion kinase

Fan

et al. 2016

Oncology Letters

Self Cite

View full text Add to dashboard Cite

Abstract. Cancer cell detachment from the primary tumor site represents the first stage of metastasis. Previous studies have identified that cell detachment is triggered by cytoskeletal disruption, which may induce a wide variety of cellular changes. Focal adhesion kinase (FAK) exhibits crucial cellular functions, including regulation of the cytoskeleton. These observations have provided exciting insights into the effect of FAK in cell detachment; however, the involvement of FAK in cell detachment remains controversial. The aim of the present study was to evaluate the effect of FAK and its function in the process of cell detachment. The results revealed that FAK expression was downregulated following trypsin treatment in human gastric, lung, colon and breast cancer cell lines, as well as a human gastric epithelial cell line. Knockdown of FAK enhanced cell detachment in gastric cancer MGC803 cells, indicating that FAK inhibits cell detachment. Further investigation revealed that trypsin induced monoubiquitination of FAK. In addition, the lysosome inhibitor, NH 4 Cl, decreased trypsin-induced degradation of FAK. Casitas B-lineage lymphoma-b (Cbl-b), an E3 ubiquitin ligase, was involved in this process, which interacted with FAK, as demonstrated by co-precipitation experiments, and promoted trypsin-induced ubiquitin-lysosome degradation of FAK. These results indicate that Cbl-b promotes cell detachment via ubiquitination of FAK. These findings provide novel insights regarding the effect of FAK and Cbl-b in the process of cancer cell detachment.

show abstract

E3 ubiquitin ligases Cbl‐b and c‐Cbl downregulate PD‐L1 in EGFR wild‐type non‐small cell lung cancer

Wang

Che

et al. 2018

FEBS Letters

Self Cite

View full text Add to dashboard Cite

Anti-PD-1/PD-L1 therapies have demonstrated prominent clinical effects in the treatment of non-small cell lung cancer (NSCLC). However, limited understanding of the regulatory mechanisms of PD-L1 has become one of the biggest challenges for further improving efficacy. In this study, we observed that in wild-type EFGR cell lines A549 and H460, the ubiquitin ligases Cbl-b and c-Cbl inhibit PD-L1 by inactivating STAT, AKT, and ERK signaling. MiR-181a and miR-940 were screened and validated to target Cbl-b and c-Cbl, respectively. Furthermore, in NSCLC tissues, the expression of Cbl-b/c-Cbl is negatively correlated with PD-L1 expression. Taken together, these findings indicated a new regulatory mechanism for PD-L1 in wild-type EGFR NSCLC cell lines by Cbl-b and c-Cbl.

show abstract

TRAIL-activated EGFR by Cbl-b-regulated EGFR redistribution in lipid rafts antagonises TRAIL-induced apoptosis in gastric cancer cells

Cited by 46 publications

References 47 publications

DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibits TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells

DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibits TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells

Cbl-b promotes cell detachment via ubiquitination of focal adhesion kinase

E3 ubiquitin ligases Cbl‐b and c‐Cbl downregulate PD‐L1 in EGFR wild‐type non‐small cell lung cancer

Contact Info

Product

Resources

About