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Annexin A2 in Inflammation and Host Defense
Open AccessArticle

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

1
Graduate Entry Medical School, University of Limerick, V94 T9PX Limerick, Ireland
2
Health Research Institute, University of Limerick and Bernal Institute, University of Limerick, V94 T9PX Limerick, Ireland
3
Stokes Laboratories, Bernal Institute, University of Limerick, V94 T9PX Limerick, Ireland
4
Department of Surgery, University Hospital Limerick, V94 F858 Limerick, Ireland
5
Lambe Institute for Translational Research, National University of Ireland Galway, H91 TK33 Galway, Ireland
6
Department of Chemical Sciences, University of Limerick, V94 T9PX Limerick, Ireland
*
Author to whom correspondence should be addressed.
Cells 2020, 9(7), 1582; https://doi.org/10.3390/cells9071582
Received: 22 May 2020 / Revised: 22 June 2020 / Accepted: 27 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue Recent Developments in Annexin Biology)
When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype. View Full-Text
Keywords: breast cancer; estrogen receptor negative; Annexin A2; mass spectrometry; metastasis breast cancer; estrogen receptor negative; Annexin A2; mass spectrometry; metastasis
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Mahdi, A.F.; Malacrida, B.; Nolan, J.; McCumiskey, M.E.; Merrigan, A.B.; Lal, A.; Tormey, S.; Lowery, A.J.; McGourty, K.; Kiely, P.A. Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers. Cells 2020, 9, 1582.

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