POPDC1 is suppressed in human breast cancer tissues and is negatively regulated by EGFR in breast cancer cell lines

Johanna Ndamwena Amunjela; Steven John Tucker

doi:10.1016/j.canlet.2017.08.002

POPDC1 is suppressed in human breast cancer tissues and is negatively regulated by EGFR in breast cancer cell lines

Johanna Ndamwena Amunjela, Steven John Tucker

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Breast cancer molecular heterogeneity has resulted in disparities in therapeutic response and targeting of molecular subtypes of breast cancer. This necessitates identification and validation of novel therapeutic targets for breast cancer treatment. Suppression of Popeye domain-containing (POPDC) proteins is hypothesized to promote malignant cell behaviour and poor clinical outcomes in various cancers. We aimed to determine whether POPDC proteins are suppressed in human ductal carcinoma tissues and if this correlates to clinical progression and Her2 status. We further assessed if the EGFR regulated POPDC1 in breast cancer. Here we show significant suppression of POPDC1 in malignant breast cancer tissues without correlation to clinical progression. Interestingly, POPDC2 and POPDC3 were highly expressed in malignant breast tissues. Furthermore, HER2+ status significantly correlated with high POPDC2 and POPDC3, but not POPDC1 expression. We further show for the first time that low POPDC1 correlates to high EGFR expression in breast cancer tissues and that EGFR negatively regulates POPDC1 expression in MCF7, MDA231 and SKBR3 breast cancer cells. Furthermore, overexpression of POPDC1 in MCF7, MDA231 and SKBR3 cells attenuated EGF-mediated cell migration and proliferation. These findings show that POPDC1 is suppressed in breast cancer and can potentially be targeted to inhibit EGFR-mediated cell migration and proliferation.

Original language	English
Pages (from-to)	81-92
Number of pages	12
Journal	Cancer Letters
Volume	406
Early online date	12 Aug 2017
DOIs	https://doi.org/10.1016/j.canlet.2017.08.002
Publication status	Published - Oct 2017

Bibliographical note

Acknowledgements
This work was funded by the University Of Aberdeen College Of Life Sciences and Medicine alongside the University of Aberdeen Elphinstone Scholarship Scheme. We thank Prof Thomas Brand and Dr Roland Schindler at Imperial College London for the plasmid constructs and collaborative efforts. We further thank Prof Valerie Speirs and Angeline Berwick at the University of Leeds and Breast Cancer Now tissue bank for the breast tissues used in technique optimisation. Finally we acknowledge Dr Jin Pu at the University of Aberdeen, for sharing the MDA231 cells.
Appendix A. Supplementary data included with online article

Keywords

POPDC1
POPDC2
POPDC3
EGFR
HER2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "POPDC1 is suppressed in human breast cancer tissues and is negatively regulated by EGFR in breast cancer cell lines",

abstract = "Breast cancer molecular heterogeneity has resulted in disparities in therapeutic response and targeting of molecular subtypes of breast cancer. This necessitates identification and validation of novel therapeutic targets for breast cancer treatment. Suppression of Popeye domain-containing (POPDC) proteins is hypothesized to promote malignant cell behaviour and poor clinical outcomes in various cancers. We aimed to determine whether POPDC proteins are suppressed in human ductal carcinoma tissues and if this correlates to clinical progression and Her2 status. We further assessed if the EGFR regulated POPDC1 in breast cancer. Here we show significant suppression of POPDC1 in malignant breast cancer tissues without correlation to clinical progression. Interestingly, POPDC2 and POPDC3 were highly expressed in malignant breast tissues. Furthermore, HER2+ status significantly correlated with high POPDC2 and POPDC3, but not POPDC1 expression. We further show for the first time that low POPDC1 correlates to high EGFR expression in breast cancer tissues and that EGFR negatively regulates POPDC1 expression in MCF7, MDA231 and SKBR3 breast cancer cells. Furthermore, overexpression of POPDC1 in MCF7, MDA231 and SKBR3 cells attenuated EGF-mediated cell migration and proliferation. These findings show that POPDC1 is suppressed in breast cancer and can potentially be targeted to inhibit EGFR-mediated cell migration and proliferation.",

keywords = "POPDC1, POPDC2, POPDC3, EGFR, HER2",

author = "Amunjela, {Johanna Ndamwena} and Tucker, {Steven John}",

note = "Acknowledgements This work was funded by the University Of Aberdeen College Of Life Sciences and Medicine alongside the University of Aberdeen Elphinstone Scholarship Scheme. We thank Prof Thomas Brand and Dr Roland Schindler at Imperial College London for the plasmid constructs and collaborative efforts. We further thank Prof Valerie Speirs and Angeline Berwick at the University of Leeds and Breast Cancer Now tissue bank for the breast tissues used in technique optimisation. Finally we acknowledge Dr Jin Pu at the University of Aberdeen, for sharing the MDA231 cells. Appendix A. Supplementary data included with online article",

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AU - Amunjela, Johanna Ndamwena

AU - Tucker, Steven John

N1 - Acknowledgements This work was funded by the University Of Aberdeen College Of Life Sciences and Medicine alongside the University of Aberdeen Elphinstone Scholarship Scheme. We thank Prof Thomas Brand and Dr Roland Schindler at Imperial College London for the plasmid constructs and collaborative efforts. We further thank Prof Valerie Speirs and Angeline Berwick at the University of Leeds and Breast Cancer Now tissue bank for the breast tissues used in technique optimisation. Finally we acknowledge Dr Jin Pu at the University of Aberdeen, for sharing the MDA231 cells. Appendix A. Supplementary data included with online article

PY - 2017/10

Y1 - 2017/10

N2 - Breast cancer molecular heterogeneity has resulted in disparities in therapeutic response and targeting of molecular subtypes of breast cancer. This necessitates identification and validation of novel therapeutic targets for breast cancer treatment. Suppression of Popeye domain-containing (POPDC) proteins is hypothesized to promote malignant cell behaviour and poor clinical outcomes in various cancers. We aimed to determine whether POPDC proteins are suppressed in human ductal carcinoma tissues and if this correlates to clinical progression and Her2 status. We further assessed if the EGFR regulated POPDC1 in breast cancer. Here we show significant suppression of POPDC1 in malignant breast cancer tissues without correlation to clinical progression. Interestingly, POPDC2 and POPDC3 were highly expressed in malignant breast tissues. Furthermore, HER2+ status significantly correlated with high POPDC2 and POPDC3, but not POPDC1 expression. We further show for the first time that low POPDC1 correlates to high EGFR expression in breast cancer tissues and that EGFR negatively regulates POPDC1 expression in MCF7, MDA231 and SKBR3 breast cancer cells. Furthermore, overexpression of POPDC1 in MCF7, MDA231 and SKBR3 cells attenuated EGF-mediated cell migration and proliferation. These findings show that POPDC1 is suppressed in breast cancer and can potentially be targeted to inhibit EGFR-mediated cell migration and proliferation.

AB - Breast cancer molecular heterogeneity has resulted in disparities in therapeutic response and targeting of molecular subtypes of breast cancer. This necessitates identification and validation of novel therapeutic targets for breast cancer treatment. Suppression of Popeye domain-containing (POPDC) proteins is hypothesized to promote malignant cell behaviour and poor clinical outcomes in various cancers. We aimed to determine whether POPDC proteins are suppressed in human ductal carcinoma tissues and if this correlates to clinical progression and Her2 status. We further assessed if the EGFR regulated POPDC1 in breast cancer. Here we show significant suppression of POPDC1 in malignant breast cancer tissues without correlation to clinical progression. Interestingly, POPDC2 and POPDC3 were highly expressed in malignant breast tissues. Furthermore, HER2+ status significantly correlated with high POPDC2 and POPDC3, but not POPDC1 expression. We further show for the first time that low POPDC1 correlates to high EGFR expression in breast cancer tissues and that EGFR negatively regulates POPDC1 expression in MCF7, MDA231 and SKBR3 breast cancer cells. Furthermore, overexpression of POPDC1 in MCF7, MDA231 and SKBR3 cells attenuated EGF-mediated cell migration and proliferation. These findings show that POPDC1 is suppressed in breast cancer and can potentially be targeted to inhibit EGFR-mediated cell migration and proliferation.

KW - POPDC1

KW - POPDC2

KW - POPDC3

KW - EGFR

KW - HER2

U2 - 10.1016/j.canlet.2017.08.002

DO - 10.1016/j.canlet.2017.08.002

M3 - Article

SN - 0304-3835

VL - 406

SP - 81

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JO - Cancer Letters

JF - Cancer Letters

ER -

POPDC1 is suppressed in human breast cancer tissues and is negatively regulated by EGFR in breast cancer cell lines

Abstract

Bibliographical note

Keywords

UN SDGs

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