Pro-invasive Effect of Proto-oncogene PBF Is Modulated by an Interaction with Cortactin.

CONTEXT: Metastatic disease is responsible for the majority of endocrine cancer deaths. New therapeutic targets are urgently needed to improve patient survival rates. OBJECTIVE: The proto-oncogene PTTG1-binding factor (PBF/PTTG1IP) is overexpressed in multiple endocrine cancers and circumstantially associated with tumor aggressiveness. This study aimed to understand the role of PBF in tumor cell invasion and identify possible routes to inhibit its action. Design, Setting, Patients, and Interventions: Thyroid, breast, and colorectal cells were transfected with PBF and cultured for in vitro analysis. PBF and cortactin (CTTN) expression was determined in differentiated thyroid cancer and The Cancer Genome Atlas RNA-seq data. PRIMARY OUTCOME MEASURE: Pro-invasive effects of PBF were evaluated by 2D Boyden chamber, 3D organotypic, and proximity ligation assays. RESULTS: Our study identified that PBF and CTTN physically interact and co-localize, and that this occurs at the cell periphery, particularly at the leading edge of migrating cancer cells. Critically, PBF induces potent cellular invasion and migration in thyroid and breast cancer cells, which is entirely abrogated in the absence of CTTN. Importantly, we found that CTTN is over-expressed in differentiated thyroid cancer, particularly in patients with regional lymph node metastasis, which significantly correlates with elevated PBF expression. Mutation of PBF (Y174A) or pharmacological intervention modulates the PBF: CTTN interaction and attenuates the invasive properties of cancer cells. CONCLUSION: Our results demonstrate a unique role for PBF in regulating CTTN function to promote endocrine cell invasion and migration, as well as identify a new targetable interaction to block tumor cell movement.

Primary hyperparathyroidism: 11-year experience in a single institute in Thailand.

Primary hyperparathyroidism (PHPT) is not an uncommon disease in the western countries. In Thailand, on the contrary, PHPT was a rare condition with various clinical presentations. All 45 PHPT patients who underwent parathyroidectomy at the Department of Surgery, Siriraj Hospital during January 1997 and December 2007 were retrospectively reviewed. Demographic data, clinical presentation, localizations imaging, operative procedures, findings, complications, and pathological reports were analyzed. Median age was 49 years (range 15-89 years) with female: male ratio of 3 : 1. Only one patient (2.2%) was asymptomatic PHPT. Of all symptomatic cases, 30 (66.7%) had skeletal symptoms, 7 (15.6%) had renal impairment, and 39 (86.7%) had mixed symptoms. 42 patients (93.3%) had parathyroid scan and all had bilateral exploration of the neck. Postoperative hungry bone syndrome was noted in 10 patients (22%). On followup, skeletal and neuropsychiatric symptoms were improved but the renal impairment was remained. The s small number of asymptomatic PHPT in our study may refer to large number of underdiagnosed PHPT in general population. The guideline for screening serum calcium for diagnosis of PHPT in Thai populations will improve the long-term consequence of the disease but will need further information to identify the target group.