C. Maenhaut
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.
Postdocs
Geneviève Dom
PhD students
María Rojo Pardillo
Nicolas Henry
Technical Support
Salima Boubkari
Publications
Selected publications
HMGA2 Overexpression in Papillary Thyroid Cancer Promotes Thyroid Cell Dedifferentiation and Invasion, and These Effects Are Counteracted by Suramin. Cindy Van Branteghem, Nicolas Henry, Ligia Craciun, Carine Maenhaut. https://doi.org/10.3390/ijms26041643
Description of a new miRNA signature for the surgical management of thyroid nodules. Quiriny M., Rodrigues Vitoria J., Saiselet M., Dom G., De Saint Aubain N., Willemse E., Digonnet A., Dequanter D., Rodriguez A., Andry G., Detours V., Maenhaut C. (2024) Cancers 16, 4214. https://doi.org/10.3390/cancers16244214
Understanding the dosage-dependent role of Dicer1 in thyroid tumorigenesis. Rojo-Pardillo, M.; Godefroid, L.; Dom, G.; Lefort, A.; Libert, F.; Robaye, B.; Maenhaut, C. International Journal of Molecular Sciences 2024, 25, 10701. https://doi.org/10.3390/ijms251910701
Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications.Jacquemin V., Antoine M., Dom G., Detours V., Maenhaut C., Dumont J.E. (2022) Cancers 14 (2) 280. https://doi.org/10.3390/cancers14020280
Thyroid cancer under the scope of emerging technologies.Tarabichi M., Demetter, P., Craciun L., Maenhaut C., Detours V. (2022) Molecular and Cellular Endocrinology 541, 111491. https://doi.org/10.1016/j.mce.2021.111491
Unraveling the roles of miR-204-5p and HMGA2 in papillary thyroid cancer tumorigenesis. Van Branteghem C., Augenlicht A., Demetter P., Craciun L., Maenhaut C. (2023) Int. J. Mol. Sci. 24, 10764. https://doi.org/10.3390/ijms241310764
Transcriptomic signature of human embryonic thyroid reveals transition from differentiation to functional maturation.Dom G., Dmitriev P., Lambot MA., Van Vliet G., Glinoer D., Libert F., Lefort A., Dumont J.E., Maenhaut C. (2021) Frontiers in Cell and Developmental Biology 9, https://doi.org/10.3389/fcell.2021.669354.
MiR-7-5p inhibits thyroid cell proliferation by targeting the EGFR/MAPK and IRS2/PI3K signaling pathways. Augenlicht A., Saiselet M., Decaussin-Petrucci M., Andry G., Dumont J.E., Maenhaut C. (2021) Oncotarget 12, 1587-1599. https://doi.org/10.18632/oncotarget.28030
Transcriptional output, cell types densities and normalization in spatial transcriptomics. Saiselet M., Rodrigues-Vitória J., Tourneur A., Craciun L., Spinette A., Larsimont D., Andry G., Lundeberg J., Maenhaut C.*, Detours V.* (*: equal contribution)(2020) Journal of Molecular Cell Biology 12, 906–908 (C. Maenhaut and V. Detours contributed equally). https://doi.org/10.3389/fcell.2021.669354
Gene expression in thyroid autonomous adenomas provides insight into their physiopathology. 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) Oncogene 24, 6902-6916.
Gene expression in human thyrocytes and autonomous adenomas reveals suppression of negative feedbacks in tumorigenesis. Van Staveren W., Weiss D., Delys, L., Venet D., Cappello M., Andry G., Dumont J.E., Libert F., Detours V., Maenhaut C. (2006) Proc. Natl. Acad. Sci, 103, 413-418.
Gene expression and the biological phenotype of papillary thyroid carcinomas. Oncogene 26, 7894-7903. Delys L., Detours V., Franc, B., Thomas G., Bogdanova T., Tronko M., Libert F., Dumont J.E., Maenhaut C. (2007)
Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers. Detours V., Delys L., Libert F., Weiss Solis D., Bogdanova T., Dumont J.E., Franc B., Thomas G., Maenhaut C. (2007) Br. J.Cancer 97, 818-825.
Human thyroid tumor cell lines derived from different tumor types present a common dedifferentiated phenotype. 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) Cancer Research 67, 8113-8120.
Human cancer cell lines: experimental models for cancer cells in situ? For cancer stem cells? Van Staveren W., Weiss D., Hebrant A., Detours V., Dumont J.E., Maenhaut C. (2009) BBA – reviews on cancer 1795, 92-103.
Thyroid gene expression in familial non-autoimmune hyperthyroidism shows common characteristics with hyperfunctioning autonomous adenomas. 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) J Clin Endocrinol Metab. 94, 2602-2609.
A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas. Dom G., Tarabichi M., Unger K., Thomas G., Oczko-Wojciechowska M., Bogdanova T., Jarzab B., Dumont J.E., Detours V., Maenhaut C. (2012) . Br. J. Cancer 107, 994-1000.
mRNA expression in papillary and anaplastic thyroid carcinoma: molecular anatomy of a killing switch. Hebrant A., Dom G., Dewaele M., Andry G., Trésallet C., Leteurtre E., Dumont J.E., Maenhaut C. (2012) PLOS ONE 7 (10), e37807.
miRNA expression in anaplastic thyroid carcinomas. 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) PLOS ONE 9 (8), e103871.
miRNA expression may account for chronic but not for acute regulation of mRNA expression in human thyroid tumor models. Floor S., Hebrant A., Pita J., Saiselet M., Trésallet C., Libert F., Andry G., Dumont J.E., van Staveren W., Maenhaut C. (2014) PLOS ONE, 9 (11), e111581.
ntratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases. 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) I Endocrine Related Cancer 22, 205-216.
microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation. Floor S., Trésallet C., Hébrant A., Desbuleux A., Libert F., Hoang C., Capello M., Andry G., van Staveren W., Maenhaut C. (2015) Molecular and Cellular Endocrinology 411, 1-10.
New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer. Saiselet M., Gacquer D., Spinette A., Craciun L., Decaussin-Petrucci M., Andry G., Detours V., Maenhaut C. (2015) BMC Genomics 16, 828.
Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution. 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) T Oncotarget 9, 10343-10359.
Distinctive desmoplastic 3D morphology associated with BRAFV600E in papillary thyroid cancers. 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) J Clin Endocrinol Metab., Jan 12. doi: 10.1210/jc.2017-02279. (C. Maenhaut and V. Detours contributed equally).
Reprogramming of energy metabolism: increased expression and roles of pyruvate carboxylase in papillary thyroid cancer. Strickaert A., Corbet C., Spinette S., Craciun L., Dom G., Andry G., Larsimont D., Wattiez R., Dumont J.E., Feron O., Maenhaut C. (2019) Thyroid 29; 845-857
5-aza-2′-deoxycytidine has minor effects on differentiation in human thyroid cancer cell lines, but modulates genes that are involved in adaptation in vitro. Dom G., Galdo V.C., Tarabichi M., Tomás G., Hebrant A., Andry G., De Martelaer V., Libert F., Leteurtre E., Dumont J.E., Maenhaut C., Van Staveren W.C.G. (2013) Thyroid 23(3), 217-228.
