ABSTRACT
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) is a member of a family of peptidyl-prolyl isomerases that specifically recognizes and binds phosphoproteins, catalyzing the rapid cis-trans isomerization of phosphorylated serine/threonine-proline motifs, which leads to changes in the structures and activities of the targeted proteins. Through this complex mechanism, PIN1 regulates many hallmarks of cancer including cell autonomous metabolism and the crosstalk with the cellular microenvironment. Many studies showed that PIN1 is largely overexpressed in cancer turning on a set of oncogenes and abrogating the function of tumor suppressor genes. Among these targets, recent evidence demonstrated that PIN1 is involved in lipid and glucose metabolism and accordingly, in the Warburg effect, a characteristic of tumor cells. As an orchestra master, PIN1 finely tunes the signaling pathways allowing cancer cells to adapt and take advantage from a poorly organized tumor microenvironment. In this review, we highlight the trilogy among PIN1, the tumor microenvironment and the metabolic program rewiring.
Subject(s)
Neoplasms , Tumor Microenvironment , Humans , NIMA-Interacting Peptidylprolyl Isomerase/genetics , NIMA-Interacting Peptidylprolyl Isomerase/metabolism , Peptidylprolyl Isomerase/genetics , Peptidylprolyl Isomerase/chemistry , Peptidylprolyl Isomerase/metabolism , Signal Transduction , PhosphorylationABSTRACT
BACKGROUND: In women with cancer-related hysterectomy, the vaginal vault cytology has a low efficacy - when performed by conventional methods - for the early detection of vaginal recurrence. The amount of exfoliated cells collected is generally low because of atrophy, and the vaginal vault corners can be so narrow that the commonly used Ayres spatula cannot often penetrate deeply into them. This prospective study aimed at identifying the advantages obtained in specimens collection using the cytobrush, as compared to the Ayres's spatula. PATIENTS AND METHODS.: 141 gynaecologic cancer patients were studied to compare samplings collected with Ayre's spatula or with cytobrush. In a pilot setting of 15 patients, vaginal cytology samples obtained by both Ayre's spatula and cytobrush were placed at the opposite sites of a single slide for quali-quantitative evaluation. Thereafter, the remaining 126 consecutive women were assigned to either group A (spatula) or B (cytobrush) according to the order of entry. The same gynaecologist performed all the procedures. RESULTS: In all 15 pilot cases, the cytobrush seemed to collect a higher quantity of material. The comparative analysis of the two complete groups indicated that the cytobrush technique was more effective than the spatula one. The odds ratio (OR) for an optimal cytology using the cytobrush was 2.8 (95% confidence interval -C.I. 1.3-6.2; chi-square test, p=0.008). CONCLUSIONS: Vaginal vault cytology with cytobrush turned out to better perform than the traditional Ayre's spatula to obtain an adequate sampling in gynecological cancer patients.