Cancers

Poster

F-2048 - BMP PATHWAY AS THE MASTER REGULATOR OF THE SLOW CYCLING, CHEMO-RESISITANT CANCER STEM CELLL COMPARTMENT IN HUMAN EPITHELIAL CARCINOMA

6/22/2018
19:00 - 20:00

Resistance to chemotherapy is a major prognostic challenge in majority of cancers. The existence of functionally distinct subpopulations in tumours, know as intra-tumour heterogeneity with differential response capacities to drugs, plays a central role in chemotherapy resistance/evasion. Cancer stem cells have been described as a major functional compartment in the heterogeneous context of tumours with major roles in tumour initiation, drug resistance and metastasis. In this study, we have used human epithelial ovarian carcinoma as a model, to analyze the molecular and cellular dynamics of tumour cells during chemotherapy response, focusing on the BMP pathway as a key player. Using in vitro and in vivo gain and loss of function assays and single-cell tracking and transcriptomic approaches, we highlighted a slow cycling subpopulation with cancer stem cell properties within tumour cells, with the capacity to resist/evade chemotherapy. We further demonstrate a key role for an autocrine bone morphogenic protein (BMP) signaling pathway as part of the maintenance network for this compartment that regulates the slow cycling/quiescent properties, chemo-resistance and epithelial-mesenchymal transition signatures. Further single cell tracking and transcriptome analyses confirm that the de novo sensitization to chemotherapy observed through inhibition of BMP pathway in the tumour cells, majorly results from release of the slow cycling cancer stem cell compartment, by adoption of active cell cycle progression patterns and chemo naïve gene signatures. Our findings strongly support a novel role for this signaling pathway at the core of chemo-resistant cancer stem cell regulation that could further refine therapy regimens through targeted therapeutic approaches.


 

Naisana Seyedasli

University of Sydney, New South Wales, Australia

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    F-2048 - BMP PATHWAY AS THE MASTER REGULATOR OF THE SLOW CYCLING, CHEMO-RESISITANT CANCER STEM CELLL COMPARTMENT IN HUMAN EPITHELIAL CARCINOMA



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