Prolactin and Growth Hormone Pathophysiology

Vincent Goffin

Team description

Our team specializes in translational approaches to unravel the intricate cellular and molecular mechanisms driving the progression and treatment resistance of breast and prostate cancers, with a particular focus on cytokine/hormone signaling and metabolic (iron) regulation of epithelial cell stemness and plasticity.

As we face the prospect of increasing cancer incidence due to extended lifespans, we emphasize the importance of early diagnosis and intervention. For localized breast and prostate tumors, surgical and radiotherapeutic treatments, combined with proactive preventive measures like PSA screening and mammography, have proven effective.

However, as these diseases advance to more complex stages, the standard of care transitions to medical treatments such as anti-androgen and anti-estrogen therapy and chemotherapy. Unfortunately, the emergence of treatment resistance is a common challenge, often leading to the progression of these cancers to metastatic stages. Drug-induced tumor cell plasticity is a key mechanism of tumor relapse.

Our research primarily revolves around three central themes:

Understanding Prostate Cancer Progression (Vincent Goffin, Jacques-Emmanuel Guidotti and Charles Dariane)
In collaboration with a consortium of biologists, bioinformaticians, and clinicians, our goal is to investigate and target the mechanisms driving the expansion of luminal progenitor-like cells in castration contexts. We aim to assess the significance of these findings in human prostate cancer specimens. This project is generously supported by a grant from the National Cancer Institute (INCa) running from November 2021 to October 2025.
Understanding Benign Prostate Hyperplasia (Vincent Goffin and Nicolas Barry-Delongchamps)
Within a consortium of biologists, immunologists, and clinicians, our mission is to map the molecular and cellular interactions between luminal progenitors and infiltrating immune cells, orchestrated by chronic STAT5 signaling in benign prostate hyperplasia. We will also explore the relevance of these findings in human BPH samples. This project is supported by a grant from the National Research Agency (ANR) spanning from March 2023 to September 2026.
Advancing Breast Cancer Research (Ahmed Hamai)
In this emerging project, we are delving into iron metabolism and the molecular mechanisms triggering ferroptosis in breast cancer stem cells (CSCs). Additionally, we will explore the role of autophagy in stemness-associated plasticity using preclinical models of breast cancer. Operational costs for this project have been generously supported for five years by the 'Ligue contre le cancer' until December 2024.

Key publications

Cosialls E, Pacreau E, Duruel C, Ceccacci S, Elhage R, Desterke C, Roger K, Guerrera C, Ducloux R, Souquere S, Pierron G, Nemazanyy I, Kelly M, Dalmas E, Chang Y, Goffin V, Mehrpour M, Hamaï A. mTOR inhibition suppresses salinomycin-induced ferroptosis in breast cancer stem cells by ironing out mitochondrial dysfunctions. Cell Death Dis. 2023; Nov 15;14(11):744. doi: 10.1038/s41419-023-06262-5. PMID: 37968262 ; PMCID: PMC10651934.

Cheradame L, Guerrera IC, Gaston J, Schmitt A, Jung V, Goudin N, Pouillard M, Radosevic-Robin N, Modesti M, Judde JG, Cairo S, Goffin V. STING protects breast cancer cells from intrinsic and genotoxic-induced DNA instability via a non-canonical, cell-autonomous pathway. Oncogene. 2021; Dec;40(49):6627-6640. doi: 10.1038/s41388-021-02037-4. PMID: 34625708 .

Bernichtein S, Pigat N, Barry Delongchamps N, Boutillon F, Verkarre V, Camparo P, Reyes-Gomez E, Méjean A, Oudard SM, Lepicard EM, Viltard M, Souberbielle JC, Friedlander G, Capiod T, Goffin V. Vitamin D3 Prevents Calcium-Induced Progression of Early-Stage Prostate Tumors by Counteracting TRPC6 and Calcium Sensing Receptor Upregulation. Cancer Res. 2017; Jan 15;77(2):355-365. doi: 10.1158/0008-5472.CAN-16-0687. PMID: 27879271 .

Sackmann Sala L, Boutillon F, Menara G, De Goyon-Pélard A, Leprévost M, Codzamanian J, Lister N, Pencik J, Clark A, Cagnard N, Bole-Feysot C, Moriggl R, Risbridger GP, Taylor RA, Kenner L, Guidotti JE, Goffin V. A rare castration-resistant progenitor cell population is highly enriched in Pten-null prostate tumours. J Pathol. 2017; Sep;243(1):51-64. doi: 10.1002/path.4924. PMID: 28603917 .

Mai TT, Hamaï A, Hienzsch A, Cañeque T, Müller S, Wicinski J, Cabaud O, Leroy C, David A, Acevedo V, Ryo A, Ginestier C, Birnbaum D, Charafe-Jauffret E, Codogno P, Mehrpour M, Rodriguez R. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem. 2017; Oct;9(10):1025-1033. doi: 10.1038/nchem.2778. PMID: 28937680 ; PMCID: PMC5890907.

Team leader