Endocrine Abstracts

Despite the increasing evidence on the relevance of the actin binding protein filamin A (FLNA) in determining an efficient intracellular response to somatostatin analogs (SSA) in pituitary tumors, there is a gap in the knowledge on the mechanisms regulating FLNA itself. FLNA is phosphorylated by PKA on Ser2152 located in a FLNA region crucial for SST2 or partner proteins binding. Although cAMP/PKA pathway plays a crucial role in GH-secreting tumors pathogenesis, the...

Adrenocortical carcinomas (ACCs) are rare endocrine tumors with poor prognosis. The insulin-like growth factor 2 (IGF2) is overexpressed in the great majority of ACC, and IGF2/IGF1R pathway acts as a proliferative autocrine loop, but to date IGF1R-targeted therapies have demonstrated a limited efficacy and the molecular mechanisms regulating this pathway are still unknown. The cytoskeleton acting-binding protein filamin A (FLNA), determinant in cancer progression and metastasi...

Cushing’s Disease (CD) is a rare condition characterized by an overproduction of ACTH by an ACTH-secreting pituitary tumor, resulting in excess of cortisol release by the adrenal glands. Pasireotide is the pituitary-targeted drug approved to treat adult patients. Its mechanism of action seems to rely on the preferential binding to the highly expressed somatostatin receptor in corticotroph tumors, SST5. Recently, somatic mutations in the deubiquitinase USP8 gene h...

The high expression of somatostatin receptor 2 (SST2) in growth hormone (GH)-secreting tumors represents the rationale for the clinical use of somatostatin analogs (SSAs) in acromegaly. However, about one third of patients displays resistance to SSAs and, to date, the responsible molecular mechanisms are still under investigation. Recently, the cytoskeletal protein Filamin A (FLNA) and the scaffolding proteins β-arrestins have emerged as key modulators of the responsivene...

Cushing’s disease (CD) is a rare disorder of chronic hypercortisolism due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor. Pasireotide, a multireceptor-targeted somatostatin (SST) analog with high binding affinity for the predominant SST receptor in human corticotroph tumors, SST5, has been recently approved to treat adult patients for whom surgery failed or does not represent a suitable option. However, to date, the molecular predictors of antisecretor...

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that originates from parafollicular thyroid C cells and accounts for 5% -10% of thyroid cancers. In all inherited cases of MTC, and in about 40% of sporadic cases, activating mutations of the receptor tyrosine kinase proto-oncogene RET are found. Constitutively active RET triggers signaling pathways involved in cell proliferation, survival and motility, but the mechanisms underlying malignant transformation of C-...

Although generally benign, pituitary tumors frequently present local invasiveness that strongly reduces neurosurgery success. We recently demonstrated a role for the actin binding protein cofilin in promoting non functioning pituitary tumors invasiveness and an inhibitory effect of dopamine receptor type 2. Somatostatin (SS) receptor type 2 (SSTR2) is the main target of pharmacological therapy of GH-secreting pituitary tumors, reducing both GH secretion and cell proliferation,...

Pulmonary neuroendocrine tumors (PNTs) comprise a spectrum of neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis. To date, the role of FLNA in PNTs aggressiveness and progression is still unknown.To address this question, we decided: i) to evaluate FLNA expression in PNTs ranging from typical carc...

SSTR2 is one of the main pharmacological target for GH-secreting pituitary adenomas treatment and the cytoskeletal protein FLNA plays an important role in tumor responsiveness by regulating SSTR2 expression and signaling. Single-Molecule Imaging was used to investigate the spatial distribution of FLNA-SSTR2 at the plasma membrane level and the involvement of FLNA in SSTR2 mobility, receptor clustering organization/internalization. This method is based on labeling SNAP/CLIP-tag...

Epi/genetic defects at the imprinted GNAS locus, that encodes the α subunit of the stimulatory G protein (Gsα), have been associated with a heterogeneous group of rare diseases, termed as Pseudohypoparathyroidism. Most GNAS-based disorders have the common feature of episodic de novo formation of heterotopic ossifications (HO) in subcutaneous tissues. The mosaic tissue distribution of HO suggests that pathogenesis involves an abnormal differentiation of precu...