Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours

Author(s)

Passaia, Barbara dos Santos ^[1] ; Lima, Keli ^[2] ; Kremer, Jean Lucas ^[1] ; da Conceicao, Barbara Brito ^[1] ; de Paula Mariani, Beatriz Marinho ^[3] ; Lipreri da Silva, Jean Carlos ^[2] ; Nogueira Zerbini, Maria Claudia ^[4] ; Barisson Villares Fragoso, Maria Candida ^[3] ; Machado-Neto, Joao Agostinho ^[2] ; Pacicco Lotfi, Claudimara Ferini ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof Lineu Prestes 2415, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Hormone & Mol Genet Lab, Sch Med, Adrenal Unit, LIM42, Hosp Clin, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Hosp Clin, Lab Liver Pathol, Div Anat Pathol, Sch Med, LIM14, Sao Paulo - Brazil

• Document type: Journal article
• Source: INVESTIGATIONAL NEW DRUGS; v. 38, n. 3, p. 899-908, JUN 2020.
• Web of Science Citations: 0

Abstract

Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highly expressed in ACC patients, and STMN1 silencing reduces the clonogenicity and migration of ACC cell lines. However, the prognostic significance of STMN1 and its therapeutic potential remain undefined in ACC. In the present study, STMN1 mRNA levels were significantly higher (p < 0.05) in ACC patients, especially in an advanced stage, and correlated with BUB1B and PINK1 expression, the prognostic-related genes in ACC. In paediatric tumours, high STMN1 expression was observed in both adrenocortical carcinoma and adrenocortical adenoma patients. Among the adult malignant tumours, STMN1 level was an independent predictor of survival outcomes (overall survival: hazard ratio = 6.08, p = 0.002; disease-free survival: hazard ratio = 4.65, p < 0.0001). Paclitaxel, a microtubule-stabilizing drug, reduces the activation of STMN1 and significantly decreases cell migration and invasion in ACC cell lines and ACC cells from secondary cell culture (all p < 0.0001). In summary, STMN1 expression may be of great value to clinical and pathological findings in therapeutic trials and deserves future studies in ACC. (AU)

• FAPESP's process: 16/17285-6 - Study of epigenetic regulation of transcription factor POD-1/TCF21in adrenocortical tumor cell cultures and its role in the cellular migration and invasion
• Grantee: Jean Lucas Kremer
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/24993-0 - Investigation of Stathmin 1 and microtubule instability in phenotype of hematological neoplasms
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/12381-7 - Identification of new targets of transcription factor POD1/TCF21 in human tumor cell cultures
• Grantee: Barbara dos Santos Passaia
• Support Opportunities: Scholarships in Brazil - Doctorate