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ERBB3 is required for metastasis formation of melanoma cells.

Tiwary S, Preziosi M, Rothberg PG, Zeitouni N, Corson N, Xu L - Oncogenesis (2014)

Bottom Line: Consistent with this, the ERBB3 ligand, NRG1, is highly expressed in mouse lungs and induces ERBB3-depdnent phosphorylation of AKT in both MA-2 and 451Lu-R cells in vitro.These findings suggest that ERBB3 may serve as a target for treating metastatic melanomas that are resistant to BIs.In support of this, administration of the pan-ERBB inhibitor, canertinib, significantly suppresses the metastasis formation of BI-resistant melanoma cell lines.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA.

ABSTRACT
Melanoma is curable when it is at an early phase but is lethal once it becomes metastatic. The recent development of BRAF(V600E) inhibitors (BIs) showed great promise in treating metastatic melanoma, but resistance developed quickly in the treated patients, and these inhibitors are not effective on melanomas that express wild-type BRAF. Alternative therapeutic strategies for metastatic melanoma are urgently needed. Here we report that ERBB3, a member of the epidermal growth factor receptor family, is required for the formation of lung metastasis from both the BI-sensitive melanoma cell line, MA-2, and the BI-resistant melanoma cell line, 451Lu-R. Further analyses revealed that ERBB3 does not affect the initial seeding of melanoma cells in lung but is required for their further development into overt metastases, indicating that ERBB3 might be essential for the survival of melanoma cells after they reach the lung. Consistent with this, the ERBB3 ligand, NRG1, is highly expressed in mouse lungs and induces ERBB3-depdnent phosphorylation of AKT in both MA-2 and 451Lu-R cells in vitro. These findings suggest that ERBB3 may serve as a target for treating metastatic melanomas that are resistant to BIs. In support of this, administration of the pan-ERBB inhibitor, canertinib, significantly suppresses the metastasis formation of BI-resistant melanoma cell lines.

No MeSH data available.


Related in: MedlinePlus

ERBB3 contributes to poor survival of melanoma patients with metastases. Fifty human metastatic melanomas were separated into two groups based on their ERBB3 expression levels. The survival probability of patients expressing high levels of ERBB3 (medium survival=5 months) was significantly lower than those expressing low levels of ERBB3 (medium survival=28 months).
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fig1: ERBB3 contributes to poor survival of melanoma patients with metastases. Fifty human metastatic melanomas were separated into two groups based on their ERBB3 expression levels. The survival probability of patients expressing high levels of ERBB3 (medium survival=5 months) was significantly lower than those expressing low levels of ERBB3 (medium survival=28 months).

Mentions: ERBB3 was found upregulated in melanoma cells with high metastatic potentials, but whether this upregulation affects patient survival has not been studied. To address this, we divided the metastases-carrying melanoma patients in our previous study5 into two groups: group 1 expresses the ERBB3 mRNA at levels higher than the median, and group 2 expresses the ERBB3 mRNA at levels lower than the median. Kaplan–Meier survival analyses were performed and showed a significant decrease in the survival of patients from group 1 (Figure 1), indicating that high levels of ERBB3 expression correlate positively to melanoma malignancy.


ERBB3 is required for metastasis formation of melanoma cells.

Tiwary S, Preziosi M, Rothberg PG, Zeitouni N, Corson N, Xu L - Oncogenesis (2014)

ERBB3 contributes to poor survival of melanoma patients with metastases. Fifty human metastatic melanomas were separated into two groups based on their ERBB3 expression levels. The survival probability of patients expressing high levels of ERBB3 (medium survival=5 months) was significantly lower than those expressing low levels of ERBB3 (medium survival=28 months).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150209&req=5

fig1: ERBB3 contributes to poor survival of melanoma patients with metastases. Fifty human metastatic melanomas were separated into two groups based on their ERBB3 expression levels. The survival probability of patients expressing high levels of ERBB3 (medium survival=5 months) was significantly lower than those expressing low levels of ERBB3 (medium survival=28 months).
Mentions: ERBB3 was found upregulated in melanoma cells with high metastatic potentials, but whether this upregulation affects patient survival has not been studied. To address this, we divided the metastases-carrying melanoma patients in our previous study5 into two groups: group 1 expresses the ERBB3 mRNA at levels higher than the median, and group 2 expresses the ERBB3 mRNA at levels lower than the median. Kaplan–Meier survival analyses were performed and showed a significant decrease in the survival of patients from group 1 (Figure 1), indicating that high levels of ERBB3 expression correlate positively to melanoma malignancy.

Bottom Line: Consistent with this, the ERBB3 ligand, NRG1, is highly expressed in mouse lungs and induces ERBB3-depdnent phosphorylation of AKT in both MA-2 and 451Lu-R cells in vitro.These findings suggest that ERBB3 may serve as a target for treating metastatic melanomas that are resistant to BIs.In support of this, administration of the pan-ERBB inhibitor, canertinib, significantly suppresses the metastasis formation of BI-resistant melanoma cell lines.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA.

ABSTRACT
Melanoma is curable when it is at an early phase but is lethal once it becomes metastatic. The recent development of BRAF(V600E) inhibitors (BIs) showed great promise in treating metastatic melanoma, but resistance developed quickly in the treated patients, and these inhibitors are not effective on melanomas that express wild-type BRAF. Alternative therapeutic strategies for metastatic melanoma are urgently needed. Here we report that ERBB3, a member of the epidermal growth factor receptor family, is required for the formation of lung metastasis from both the BI-sensitive melanoma cell line, MA-2, and the BI-resistant melanoma cell line, 451Lu-R. Further analyses revealed that ERBB3 does not affect the initial seeding of melanoma cells in lung but is required for their further development into overt metastases, indicating that ERBB3 might be essential for the survival of melanoma cells after they reach the lung. Consistent with this, the ERBB3 ligand, NRG1, is highly expressed in mouse lungs and induces ERBB3-depdnent phosphorylation of AKT in both MA-2 and 451Lu-R cells in vitro. These findings suggest that ERBB3 may serve as a target for treating metastatic melanomas that are resistant to BIs. In support of this, administration of the pan-ERBB inhibitor, canertinib, significantly suppresses the metastasis formation of BI-resistant melanoma cell lines.

No MeSH data available.


Related in: MedlinePlus