Articles: signal-transducing-adaptor-proteins.
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The present study aimed to detect the A-kinase interacting protein 1 (AKIP1) expression in clear cell renal cell carcinoma (ccRCC) tumor tissues and adjacent tissues, and further investigate the correlation of tumor AKIP1 expression with clinicopathological features and survival profile in ccRCC patients. Totally 210 ccRCC patients who underwent resection were retrospectively reviewed, and their tumor and adjacent tissue specimens were acquired for immunohistochemical detection of AKIP1 expression. The survival data of patients were collected for overall survival (OS) assessment. ⋯ OS was the lowest in the patients with AKIP1 high+++ expression, followed by those with AKIP1 high++ expression and AKIP1 high+ expression, and then patients with AKIP1 low expression (P < .001). Furthermore, multivariate Cox regression exhibited tumor AKIP1 high expression (P = .017), age (>60 years) (P = .030), pathological grade (G2/G3 vs G1) (P = .037), and TNM stage (II/III vs I) (P < .001) were independent predictive factors for decreased OS in ccRCC patients. AKIP1 presents potency to be a novel biomarker for tumor progression and prognosis surveillance in ccRCC.
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The Hippo pathway and its effector protein YAP (a transcriptional coactivator) have been identified as important in the biology of both hepatocellular carcinoma and cholangiocarcinoma. First identified as a tumor suppressor pathway in Drosophila, the understanding of the mammalian YAP signaling and its regulation continues to expand. In its "on" function, the canonical regulatory Hippo pathway, a well-described serine/threonine kinase module, regulates YAP function by restricting its subcellular localization to the cytoplasm. ⋯ These represent positive regulatory events that may be targetable. Additionally, several groups have identified potentiating feed-forward signaling for YAP in multiple contexts, suggesting other experimental therapeutic approaches to interrupt these signaling loops. Herein we explore the current data supporting alternative YAP regulatory pathways, review the described feed-forward signaling cascades that are YAP dependent, and explore targeting strategies that have been employed in preclinical models of hepatic malignancies.
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Previously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. ⋯ SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.
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Aim of the study: To assess serum sclerostin in transfusion-dependent beta-thalassaemia patients versus healthy controls and to examine its associations with bone mineral density, bone metabolism markers and beta thalassaemia alterations. Material and methods: Sixty-two transfusion-dependent beta-thalassaemia (TDßT) patients and 30 healthy controls were evaluated for serum sclerostin, osteocalcin, beta-cross laps, osteoprotegerin and serum level of receptor activator of nuclear factor kappa-Β ligand (sRANKL). Bone mineral density was measured at the lumbar spine and femoral neck. ⋯ Serum sclerostin is negatively associated with bone mineral density and the bone synthesis markers and positively with the bone resorption indices. Serum sclerostin is significantly associated with pre-transfusion haemoglobin, liver iron concentration, splenectomy status and fragility fracture events in adult patients with transfusion-dependent beta-thalassaemia. Serum sclerostin could serve as a marker of severe osteoporosis in beta-thalassaemia patients.
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Am. J. Clin. Pathol. · Apr 2020
Expression and Prognostic Value of IFIT1 and IFITM3 in Head and Neck Squamous Cell Carcinoma.
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) and interferon-induced transmembrane protein 3 (IFITM3) are commonly induced by type I interferon. The study aims to investigate the expression and clinical significance of IFIT1 and IFITM3 in head and neck squamous cell carcinoma (HNSCC). ⋯ IFIT1 and IFITM3 were overexpressed in HNSCC and indicated poor prognoses for patients with HNSCC. IFIT1 and IFITM3 expression was correlated with several immune checkpoint molecules and tumor-associated macrophage markers.