Our research
Thyroid Cancer group – Research activities
Our research aims to better understand the genetic changes underlying carcinogenesis and tumor progression in thyroid cancers, by defining the molecular phenotype of these cancers.
Background
Tumors originating from thyroid follicular cells are the most frequent endocrine tumors with an increasing incidence that will make this cancer one of the most common in women in the next decade. They comprise a spectrum of well-defined morphological phenotypes with variable rates of growth, differentiation and biological aggressiveness. They include benign follicular adenomas and malignant carcinomas, further subdivided in follicular (FTC) or papillary (PTC) carcinomas, still partly differentiated. Both of which may evolve in anaplastic carcinoma (ATC), totally dedifferentiated. While PTC (85 % of the thyroid cancers) and FTC have a relatively good prognosis and can mostly be treated with surgery and I131, ATC are lethal within six months and do not respond to any therapy (surgery, chemotherapy, I131). ATC are responsible for half of the thyroid cancer related deaths and are one of the most aggressive cancers. They are representative of finally evolving cancers in general.
Among the very common thyroid nodules (up to 40% beyond 50 years), only 5% are found to be malignant. Fine-needle aspiration (FNA) is routinely used in the preoperative evaluation of these nodules. However, 15% to 30% of aspirations yield inconclusive cytological findings. Many patients therefore are operated, three out of four unnecessarily.
The clinical evolution of thyroid tumors thus varies extremely according to their type, and a reliable diagnosis for the various sub-types of tumors to select adequate treatments as well as new therapeutic tools are highly required.
Figure: Thyroid tumorigenesis, altered signaling pathways and main mutations
Since several years, we are defining in molecular terms the pathways involved in the control of the proliferation of normal thyroid cells and in the perversion of this process in thyroid tumors.
In recent years, the role of miRNAs, small non-coding RNAs of 19-25 nucleotides that negatively regulate mRNAs, in various pathologies has been increasingly documented and aberrant expression of miRNAs is often correlated with tumor development. For thyroid cancers, while papillary and follicular cancers present up and downregulated miRNAs, anaplastic carcinomas show almost exclusively downregulated miRNAs, suggesting that the progression of differentiated thyroid carcinomas to less differentiated forms is characterized by drastic changes in miRNA expressions. Furthermore, downregulation or inactivating mutations of Dicer1, a type III ribonuclease involved in miRNA biogenesis, have been described in thyroid and other cancers and are associated with aggressive features.
Research activities
The research that we are currently carrying out has a fundamental aspect and a diagnostic aspect: it aims on the one hand to better understand the functional role of miRNAs and Dicer1 in thyroid tumorigenesis, and on the other hand to analyze the potential of these miRNAs as biomarkers to distinguish between benign and malignant thyroid tumors.
To address these questions, we use various molecular and cellular biology approaches. We investigate human thyroid cancer samples and thyroid tumor models: in vitro cell cultures and in vivo transgenic mice.
Group members
Carine Maenhaut, PI (Carine.Maenhaut@ulb.be)
Phone # +32 (0)2 555 4137
Postdocs
Geneviève Dom
PhD students
Ludivine Godefroid
Maria Rojo Pardillo
Nicolas Henry
Technical Support
Salima Boubkari
Publications
Selected publications
Tarabichi M., Demetter, P., Craciun L., Maenhaut C., Detours V. (2022) Thyroid cancer under the scope of emerging technologies. Molecular and Cellular Endocrinology 541, 111491.
Van Branteghem C., Augenlicht A., Demetter P., Craciun L., Maenhaut C. (2023) Unraveling the roles of miR-204-5p and HMGA2 in papillary thyroid cancer tumorigenesis. Int. J. Mol. Sci. 24, 10764
Dom G., Dmitriev P., Lambot MA., Van Vliet G., Glinoer D., Libert F., Lefort A., Dumont J.E., Maenhaut C. (2021) Transcriptomic signature of human embryonic thyroid reveals transition from differentiation to functional maturation. Frontiers in Cell and Developmental Biology 9, https://doi.org/10.3389/fcell.2021.669354.
Augenlicht A., Saiselet M., Decaussin-Petrucci M., Andry G., Dumont J.E., Maenhaut C. (2021) MiR-7-5p inhibits thyroid cell proliferation by targeting the EGFR/MAPK and IRS2/PI3K signaling pathways. Oncotarget 12, 1587-1599.
Saiselet M., Rodrigues-Vitória J., Tourneur A., Craciun L., Spinette A., Larsimont D., Andry G., Lundeberg J., Maenhaut C.*, Detours V.* (*: equal contribution)(2020) Transcriptional output, cell types densities and normalization in spatial transcriptomics. Journal of Molecular Cell Biology 12, 906–908 (C. Maenhaut and V. Detours contributed equally).
Wattel S., Mircescu H., Venet, D., Burniat A., Franc, B., Frank S., Andry, G., Van Sande J., Rocmans P., Dumont J.E., Detours V., Maenhaut C. (2005) Gene expression in thyroid autonomous adenomas provides insight into their physiopathology. Oncogene 24, 6902-6916.
van Staveren W., Weiss D., Delys, L., Venet D., Cappello M., Andry G., Dumont J.E., Libert F., Detours V., Maenhaut C. (2006) Gene expression in human thyrocytes and autonomous adenomas reveals suppression of negative feedbacks in tumorigenesis. Proc. Natl. Acad. Sci, 103, 413-418.
Delys L., Detours V., Franc, B., Thomas G., Bogdanova T., Tronko M., Libert F., Dumont J.E., Maenhaut C. (2007) Gene expression and the biological phenotype of papillary thyroid carcinomas. Oncogene 26, 7894-7903.
Detours V., Delys L., Libert F., Weiss Solis D., Bogdanova T., Dumont J.E., Franc B., Thomas G., Maenhaut C. (2007) Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers. Br. J.Cancer 97, 818-825.
van Staveren W., Weiss D., Delys L., Duprez L., Andry, G., Franc B., Thomas G., Libert F., Dumont J.E., Detours V., Maenhaut C. (2007) Human thyroid tumor cell lines derived from different tumor types present a common dedifferentiated phenotype. Cancer Research 67, 8113-8120.
van Staveren W., Weiss D., Hebrant A., Detours V., Dumont J.E., Maenhaut C. (2009) Human cancer cell lines: experimental models for cancer cells in situ? For cancer stem cells? BBA – reviews on cancer 1795, 92-103.
Hebrant A., Van Sande J., Roger P., Patey M., Klein M., Bournaud C., Savagner F., Leclere J., Dumont J.E., van Staveren, W., Maenhaut C. (2009) Thyroid gene expression in familial non-autoimmune hyperthyroidism shows common characteristics with hyperfunctioning autonomous adenomas. J Clin Endocrinol Metab. 94, 2602-2609.
Dom G., Tarabichi M., Unger K., Thomas G., Oczko-Wojciechowska M., Bogdanova T., Jarzab B., Dumont J.E., Detours V., Maenhaut C. (2012) A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas. Br. J. Cancer 107, 994-1000.
Hebrant A., Dom G., Dewaele M., Andry G., Trésallet C., Leteurtre E., Dumont J.E., Maenhaut C. (2012) mRNA expression in papillary and anaplastic thyroid carcinoma: molecular anatomy of a killing switch. PLOS ONE 7 (10), e37807.
Hebrant A., Floor S., Saiselet M., Antoniou A., Desbuleux A., Snyers B., La C., de Saint Aubain N., Leteurtre E., Andry G., Maenhaut C. (2014) miRNA expression in anaplastic thyroid carcinomas. PLOS ONE 9 (8), e103871.
Floor S., Hebrant A., Pita J., Saiselet M., Trésallet C., Libert F., Andry G., Dumont J.E., van Staveren W., Maenhaut C. (2014) miRNA expression may account for chronic but not for acute regulation of mRNA expression in human thyroid tumor models. PLOS ONE, 9 (11), e111581.
Le Pennec S., Konopka T., Gacquer D., Fimereli D., Tarabichi M., Tomás G., Savagner F., Decaussin-Petrucci M., Trésallet C., Andry G., Larsimont D., Detours V., Maenhaut C. (2015) Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases. Endocrine Related Cancer 22, 205-216.
Floor S., Trésallet C., Hébrant A., Desbuleux A., Libert F., Hoang C., Capello M., Andry G., van Staveren W., Maenhaut C. (2015) microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation. Molecular and Cellular Endocrinology 411, 1-10.
Saiselet M., Gacquer D., Spinette A., Craciun L., Decaussin-Petrucci M., Andry G., Detours V., Maenhaut C. (2015) New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer. BMC Genomics 16, 828.
Dom G., Frank S., Floor S., Kehagias P., Libert F., Hoang C., Andry G., Spinette A., Craciun L., de Saint Aubin N., Tresallet C., Tissier F., Savagner F., Majjaj S., Gutierrez-Roelens I., Marbaix E., Dumont J.E., Maenhaut C. (2018) Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution. Oncotarget 9, 10343-10359.
Tarabichi M., Antoniou A., Le Pennec S., Gacquer D., de Saint Aubain N., Craciun L., Cielen T., Laios I., Larsimont D., Andry G., Dumont J.E., Maenhaut C., Detours V. (2018) Distinctive desmoplastic 3D morphology associated with BRAFV600E in papillary thyroid cancers. J Clin Endocrinol Metab., Jan 12. doi: 10.1210/jc.2017-02279. (C. Maenhaut and V. Detours contributed equally).
Strickaert A., Corbet C., Spinette S., Craciun L., Dom G., Andry G., Larsimont D., Wattiez R., Dumont J.E., Feron O., Maenhaut C. (2019) Reprogramming of energy metabolism: increased expression and roles of pyruvate carboxylase in papillary thyroid cancer. Thyroid 29; 845-857