Poster Presentation 35th Lorne Cancer Conference 2023

SULF1 is highly expressed at Epithelial Mesenchymal Transition (EMT)/MET state of triple negative breast cancer and is a novel therapeutic target to reduce metastasis of TNBC (#140)

Narjis Fatima 1 2 , Felix Kohane 1 2 3 , Beatriz Perez San Juan 1 2 , Heloisa Helena Milioli 1 2 , John Lock 3 , Vanina Rodriguez 1 2 , Christine Chaffer 1 2
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW , Australia
  3. School of Medical Sciences, University of New South Wales, Sydney, NSW , Australia


Breast cancer is the most frequently diagnosed cancer in females worldwide. Triple negative breast cancer (TNBC) is one of the most aggressive kinds of breast cancer due to its heterogenous nature, propensity to metastasise and shift towards epithelial-mesenchymal transition (EMT). Studies have demonstrated that cancer stem cells (CSCs) in the hybrid state of EMT/MET exhibit increased tumorigenicity, and expresses higher levels of an enzyme called sulfatase 1 (SULF1).

We hypothesised that SULF1 is essential for the maintenance of the CSC state, and reducing its expression will drive cells towards mesenchymal epithelial transition (MET), hence mitigating TNBC’s metastatic potential. Further on, we also hypothesised that reducing SULF1 expression will change the inflammatory response in aggressive tumours due to changes in EMT-inducing cytokines in the tumour microenvironment.


We used single cell imaging to identify different cell states across the EMT spectrum in heterogenous TNBC cell line models. Dimension reduction techniques were performed to classify E/M subpopulations. Random Forests machine learning models were utilised to predict E/M cell states and effects of SULF1. In vitro and in vivo knock down models were created to study the effect of SULF1 modulation on CSC function. Transcriptomic changes were analysed using RNA-seq. Inflammatory response was studied in vivo and changes in tumours were assessed using FACS and IHC.


We confirmed that CSCs in the hybrid state expresses higher levels of SULF1 and its downregulation inhibits CSC function through blocking tumour initiation and metastatic potential. In vitro knockdown of SULF1 induced an actin cytoskeleton reorganization and cell clustering, concomitant with higher expression of the epithelial marker CDH1. RNA-seq data showed significant upregulation of Interferon-Alpha and Gamma signalling pathways and downregulation of EMT, Androgen response, MTORC1 signalling in SULF1 knockdown models.


We showed that reduced levels of SULF1 drive cells into MET and is important in controlling metastatic potential of TNBC. We are currently studying the effect of SULF1 KD on inflammation. Our future work is inclined to demonstrate the efficacy of SULF1 inhibition in combination with chemotherapy/immunotherapy in TNBC. Based on these results, inhibiting SULF1 maybe a good strategy to treat TNBC patients.