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PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , |
| In: | Cancer Research, 77, 2017, 1, S. 187-197 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Zhou, Xiaorong Updegraff, Barrett L. Guo, Yabin Peyton, Michael Girard, Luc Larsen, Jill E. Xie, Xian-Jin Zhou, Yunyun Hwang, Tae Hyun Xie, Yang Rodriguez-Canales, Jaime Villalobos, Pamela Behrens, Carmen Wistuba, Ignacio I. Minna, John D. O'Donnell, Kathryn A. Zhou, Xiaorong Updegraff, Barrett L. Guo, Yabin Peyton, Michael Girard, Luc Larsen, Jill E. Xie, Xian-Jin Zhou, Yunyun Hwang, Tae Hyun Xie, Yang Rodriguez-Canales, Jaime Villalobos, Pamela Behrens, Carmen Wistuba, Ignacio I. Minna, John D. O'Donnell, Kathryn A. |
|---|---|
| author |
Zhou, Xiaorong Updegraff, Barrett L. Guo, Yabin Peyton, Michael Girard, Luc Larsen, Jill E. Xie, Xian-Jin Zhou, Yunyun Hwang, Tae Hyun Xie, Yang Rodriguez-Canales, Jaime Villalobos, Pamela Behrens, Carmen Wistuba, Ignacio I. Minna, John D. O'Donnell, Kathryn A. |
| spellingShingle |
Zhou, Xiaorong Updegraff, Barrett L. Guo, Yabin Peyton, Michael Girard, Luc Larsen, Jill E. Xie, Xian-Jin Zhou, Yunyun Hwang, Tae Hyun Xie, Yang Rodriguez-Canales, Jaime Villalobos, Pamela Behrens, Carmen Wistuba, Ignacio I. Minna, John D. O'Donnell, Kathryn A. Cancer Research PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis Cancer Research Oncology |
| author_sort |
zhou, xiaorong |
| spelling |
Zhou, Xiaorong Updegraff, Barrett L. Guo, Yabin Peyton, Michael Girard, Luc Larsen, Jill E. Xie, Xian-Jin Zhou, Yunyun Hwang, Tae Hyun Xie, Yang Rodriguez-Canales, Jaime Villalobos, Pamela Behrens, Carmen Wistuba, Ignacio I. Minna, John D. O'Donnell, Kathryn A. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-16-1267-t <jats:title>Abstract</jats:title> <jats:p>Non–small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths worldwide. Given the efficacy of membrane proteins as therapeutic targets in human malignancies, we examined cell-surface receptors that may act as drivers of lung tumorigenesis. Here, we report that the PROTOCADHERIN PCDH7 is overexpressed frequently in NSCLC tumors where this event is associated with poor clinical outcome. PCDH7 overexpression synergized with EGFR and KRAS to induce MAPK signaling and tumorigenesis. Conversely, PCDH7 depletion suppressed ERK activation, sensitized cells to MEK inhibitors, and reduced tumor growth. PCDH7 potentiated ERK signaling by facilitating interaction of protein phosphatase PP2A with its potent inhibitor, the SET oncoprotein. By establishing an oncogenic role for PCDH7 in lung tumorigenesis, our results provide a rationale to develop novel PCDH7 targeting therapies that act at the cell surface of NSCLC cells to compromise their growth. Cancer Res; 77(1); 187–97. ©2016 AACR.</jats:p> PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis Cancer Research |
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| title |
PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_unstemmed |
PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_full |
PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_fullStr |
PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_full_unstemmed |
PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_short |
PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_sort |
protocadherin 7 acts through set and pp2a to potentiate mapk signaling by egfr and kras during lung tumorigenesis |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-16-1267-t |
| publishDate |
2017 |
| physical |
187-197 |
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<jats:title>Abstract</jats:title>
<jats:p>Non–small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths worldwide. Given the efficacy of membrane proteins as therapeutic targets in human malignancies, we examined cell-surface receptors that may act as drivers of lung tumorigenesis. Here, we report that the PROTOCADHERIN PCDH7 is overexpressed frequently in NSCLC tumors where this event is associated with poor clinical outcome. PCDH7 overexpression synergized with EGFR and KRAS to induce MAPK signaling and tumorigenesis. Conversely, PCDH7 depletion suppressed ERK activation, sensitized cells to MEK inhibitors, and reduced tumor growth. PCDH7 potentiated ERK signaling by facilitating interaction of protein phosphatase PP2A with its potent inhibitor, the SET oncoprotein. By establishing an oncogenic role for PCDH7 in lung tumorigenesis, our results provide a rationale to develop novel PCDH7 targeting therapies that act at the cell surface of NSCLC cells to compromise their growth. Cancer Res; 77(1); 187–97. ©2016 AACR.</jats:p> |
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| author | Zhou, Xiaorong, Updegraff, Barrett L., Guo, Yabin, Peyton, Michael, Girard, Luc, Larsen, Jill E., Xie, Xian-Jin, Zhou, Yunyun, Hwang, Tae Hyun, Xie, Yang, Rodriguez-Canales, Jaime, Villalobos, Pamela, Behrens, Carmen, Wistuba, Ignacio I., Minna, John D., O'Donnell, Kathryn A. |
| author_facet | Zhou, Xiaorong, Updegraff, Barrett L., Guo, Yabin, Peyton, Michael, Girard, Luc, Larsen, Jill E., Xie, Xian-Jin, Zhou, Yunyun, Hwang, Tae Hyun, Xie, Yang, Rodriguez-Canales, Jaime, Villalobos, Pamela, Behrens, Carmen, Wistuba, Ignacio I., Minna, John D., O'Donnell, Kathryn A., Zhou, Xiaorong, Updegraff, Barrett L., Guo, Yabin, Peyton, Michael, Girard, Luc, Larsen, Jill E., Xie, Xian-Jin, Zhou, Yunyun, Hwang, Tae Hyun, Xie, Yang, Rodriguez-Canales, Jaime, Villalobos, Pamela, Behrens, Carmen, Wistuba, Ignacio I., Minna, John D., O'Donnell, Kathryn A. |
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| description | <jats:title>Abstract</jats:title> <jats:p>Non–small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths worldwide. Given the efficacy of membrane proteins as therapeutic targets in human malignancies, we examined cell-surface receptors that may act as drivers of lung tumorigenesis. Here, we report that the PROTOCADHERIN PCDH7 is overexpressed frequently in NSCLC tumors where this event is associated with poor clinical outcome. PCDH7 overexpression synergized with EGFR and KRAS to induce MAPK signaling and tumorigenesis. Conversely, PCDH7 depletion suppressed ERK activation, sensitized cells to MEK inhibitors, and reduced tumor growth. PCDH7 potentiated ERK signaling by facilitating interaction of protein phosphatase PP2A with its potent inhibitor, the SET oncoprotein. By establishing an oncogenic role for PCDH7 in lung tumorigenesis, our results provide a rationale to develop novel PCDH7 targeting therapies that act at the cell surface of NSCLC cells to compromise their growth. Cancer Res; 77(1); 187–97. ©2016 AACR.</jats:p> |
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| spelling | Zhou, Xiaorong Updegraff, Barrett L. Guo, Yabin Peyton, Michael Girard, Luc Larsen, Jill E. Xie, Xian-Jin Zhou, Yunyun Hwang, Tae Hyun Xie, Yang Rodriguez-Canales, Jaime Villalobos, Pamela Behrens, Carmen Wistuba, Ignacio I. Minna, John D. O'Donnell, Kathryn A. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-16-1267-t <jats:title>Abstract</jats:title> <jats:p>Non–small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths worldwide. Given the efficacy of membrane proteins as therapeutic targets in human malignancies, we examined cell-surface receptors that may act as drivers of lung tumorigenesis. Here, we report that the PROTOCADHERIN PCDH7 is overexpressed frequently in NSCLC tumors where this event is associated with poor clinical outcome. PCDH7 overexpression synergized with EGFR and KRAS to induce MAPK signaling and tumorigenesis. Conversely, PCDH7 depletion suppressed ERK activation, sensitized cells to MEK inhibitors, and reduced tumor growth. PCDH7 potentiated ERK signaling by facilitating interaction of protein phosphatase PP2A with its potent inhibitor, the SET oncoprotein. By establishing an oncogenic role for PCDH7 in lung tumorigenesis, our results provide a rationale to develop novel PCDH7 targeting therapies that act at the cell surface of NSCLC cells to compromise their growth. Cancer Res; 77(1); 187–97. ©2016 AACR.</jats:p> PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis Cancer Research |
| spellingShingle | Zhou, Xiaorong, Updegraff, Barrett L., Guo, Yabin, Peyton, Michael, Girard, Luc, Larsen, Jill E., Xie, Xian-Jin, Zhou, Yunyun, Hwang, Tae Hyun, Xie, Yang, Rodriguez-Canales, Jaime, Villalobos, Pamela, Behrens, Carmen, Wistuba, Ignacio I., Minna, John D., O'Donnell, Kathryn A., Cancer Research, PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis, Cancer Research, Oncology |
| title | PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_full | PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_fullStr | PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_full_unstemmed | PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_short | PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| title_sort | protocadherin 7 acts through set and pp2a to potentiate mapk signaling by egfr and kras during lung tumorigenesis |
| title_unstemmed | PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-16-1267-t |