Department of Tumor Biology
Dr. Lidereau's BCRF-funded study focuses on breast cancers that spread (metastasize) to the lung and bone. Her aims are to identify and molecularly characterize the genes involved in breast cancer organ-specific metastasis. Such knowledge would help to plan care for patients, giving information to select new targets for emerging preventive treatments and contributing to avoid overtreatment in specific cases. In 2013-2014, Dr. Lidereau will continue to pursue the functional study of KIND1 gene in breast cancer lung metastasis. In addition to the ongoing tests (e.g. microarray analyses, migration/invasion assays, identification of the corresponding molecular pathways, etc.), Dr. Lidereau plans to use state-of-the art cell biology techniques (including time-lapse microscopy).
Also, to gain new insight into bone metastasis, Dr. Lidereau has re-interpreted the biological meaning of their transcriptomic data to identifying relevant molecular pathways. She will further examine the variation of the expression profiles of single genes and molecular pathways in bone metastasizing tumors, as well as pursue the functional analysis of newly selected molecular markers associated with bone metastasis. These studies will determine the probability and extent of metastatic spread to different organs: metastasis to bone being a concern for long-term morbidity, and metastasis to visceral tissues a serious concern.
During the first period of the BCRF grant 2013-2014, Dr. Lidereau’s team focused efforts on lung metastasis of breast cancer. In particular, they further investigated the mechanistic role of kindlin-1 in breast tumor growth and metastasis.
First, they demonstrated that Kindlin-1 interaction with β1-integrin is necessary for the cell migration but is dispensable for its proliferative function. Indeed, using an integrin-binding defective mutant of kindlin-1, the researchers demonstrated that this mutant form of the protein was able to sustain high proliferation rate in tumor cells. They then investigated the cellular mechanisms leading to kindlin-1-mediated genomic instability. Kindlin-1 overexpressing cells, monitored by time-lapse live-cell imaging, took an unusually long time to finish their division process, displaying marked difficulties in completing the separation into two daughter cells. Finally, they showed that kindlin-1 expression is correlated to genomic instability in breast cancer cell lines and planed a similar analysis in a series of breast tumors.
In conclusion, Kindlin-1 is emerging as a multifaceted key player in cell malignancy. Its over-expression triggers proliferation, migration and genome instability, all essential hallmarks of cancer progression.
Dr. Rosette Lidereau received her PhD (1987) from Paris University, France. From 1992 - 2013 she served as a Research Director of the INSERM (Institut National des Sciences et de la Recherche Médicale), where from 2000-2013 she was in charge of the head of the INSERM Unit 735, located in the Institut Curie / Hopital René Huguenin (IC/HRH), Saint-Cloud, France. Currently she is a Research Director in the department of tumor biology at Institut Curie, Paris. IC/HRH is a non-profit institution dedicated to cancer with a history of medical and biological expertise in breast cancer.
Dr. Lidereau's scientific career has focused on the biology of breast cancer. Her research interests are the evaluation of oncogenes' implication in breast tumorigenesis and their impact in the clinic as prognostic and predictive factors in breast cancer.