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J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21 Page 8 of 36

10. Relevance of FoxO3a in tamoxifen resistant breast cancer

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Catia Morelli , Marco Fiorillo , Pietro Rizza , Michele Pellegrino , Alessandra Nigro , Elena Ricci , Marilena
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Lanzino , Michael Lisanti , Sebastiano Andò , Diego Sisci 1
1 Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende, Cosenza
87036, Italy.
2 Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC),
University of Salford, Greater Manchester M5 4WT, UK.
Resistance to endocrine treatments is a major clinical challenge in the management of estrogen receptor
positive (ER+) breast cancers (BC). Although multiple mechanisms leading to endocrine resistance have
been proposed, the poor outcome of this subgroup of BC patients demands additional studies. Here
we show that the expression of FoxO3a transcription factor is reduced in ER+ BC cells that developed
resistance to Tamoxifen (Tam), TamR cells, due to its hyper-phosphorylation and degradation mediated
by a hyperactive ERK1/2 pathway. On the other hand, FoxO3a silencing counteracts Tam induced growth
inhibition in wtMCF-7, demonstrating that FoxO3a is a mediator of cell response to Tam.

FoxO3a re-activation in TamR/FoxO3a inducible clones, developed to express a constitutively active
FoxO3a under tetracyclines control, re-established the sensitivity to the antiestrogen, inhibiting
proliferation and cell cycle progression, as well as restoring Tam dependent apoptotic response.

Proteomics analysis unveiled novel interesting and potential mediators of the anti-proliferative and pro-
apoptotic activity of the transcription factor, while Kaplan-Meier survival curves showed that high levels of
FoxO3a transcripts strongly correlate to a positive response to Tam therapy in BC patients. Finally, FoxO3a
induction by the anti-convulsant Lamotrigine (LTG), strongly reduced tumor mass in TamR-derived mouse
xenografts.

Altogether, our data indicate that FoxO3a is a good prognostic factor in ER+ BC, predicting a positive
response to endocrine therapy, and a key target to be exploited in combination therapy. In this context,
LTG might represent a valid candidate to be used as an adjuvant to Tam therapy in patients at risk.

Biography
Catia Morelli has completed her PhD from University of Calabria, Cosenza, Italy, after a 4 years training
period (1999-2003) at the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (USA).
She is now Researcher at the Department of Pharmacy and Health and Nutritional Sciences at the
University of Calabria, recently awaded as Department of Excellence by the Italian Ministry of Education,
University and Research. She encounters more than 35 papers in reputed journals and she is also co-
founder of NanoSiliCal Devices, a spin-off company of the University of Calabria, developing silica-based
nanosystems to be employed in targeted therapy (http://www.nanosilicaldevices.com/en/).

11. Deciphering human B cell repertoire with next-generation sequencing technology

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DuckKyun Yoo , Wonjun Yang , Kihyun Kim , Sangil Kim , Sung Min Kim , Hyori Kim , Jinhee Kim , So
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Young Chang , Meehyun Ko , Ji-Young Min , Haejun Han , Taehoon Ryu , Jungeun Kim , Junho Chung 1,5,6
1 Seoul National University College of Medicine, Seoul 03080, South Korea.
2 Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, South Korea.