Corrigendum to "Recognition motifs for importin 4 [(L)PPRS(G/P)P] and importin 5 [KP(K/Y)LV] binding, identified by bio-informatic simulation and experimental in vitro validation" [Comput Struct Biotechnol J 20 (2022) 5952-5961]

Nuclear translocation of large proteins is mediated through karyopherins, carrier proteins recognizing specific motifs of cargo proteins, known as nuclear localization signals (NLS). However, only few NLS signals have been reported until now. In the present work, NLS signals for Importins 4 and 5 were identified through an unsupervised in silico approach, followed by experimental in vitro validation. The sequences LPPRS(G/P)P and KP(K/Y)LV were identified and are proposed as recognition motifs for Importins 4 and 5 binding, respectively. They are involved in the trafficking of important proteins into the nucleus. These sequences were validated in the breast cancer cell line T47D, which expresses both Importins 4 and 5. Elucidating the complex relationships of the nuclear transporters and their cargo proteins is very important in better understanding the mechanism of nuclear transport of proteins and laying the foundation for the development of novel therapeutics, targeting specific importins

Increased Serum Apelin Levels in Patients with Inflammatory Bowel Disease

Apelin has been implicated in the pathogenesis of several chronic inflammatory diseases through mechanisms related to endothelial cells dysfunction. There is evidence of increased apelin levels in mesenteric adipose tissue and colonic epithelium in patients with inflammatory bowel disease (IBD), but their significance remains unclear. We aimed to measure serum apelin (SA) levels in patients with IBD and to evaluate an association with disease characteristics. SA levels of 104 IBD patients and age and sex matched healthy controls (HCs) in a 1:1 ratio were compared. SA-13 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Mean SA levels were increased in IBD patients compared to HCs (1996.29 ± 1592.96 pg/mL vs. 1552.99 ± 809.64 pg/mL, p = 0.012). Both patients without and with cardiovascular disease (CVD) had increased SA levels (2076.44 ± 1714.74 pg/mL vs. 1525.75 ± 818.74 pg/mL, p = 0.011 and 1743.01 ± 1116.26 pg/mL vs. 1283.92 ± 726.85 pg/mL, p = 0.035, respectively). An inverse association between mean SA levels and a history of musculoskeletal extraintestinal manifestations in the subgroup of IBD patients without CVD was found (p = 0.043). The present study—the first to evaluate SA levels in patients with IBD—showed that IBD patients have higher levels of SA compared to HCs. The potential role of SA in IBD merits further investigation in larger studies

BCMA (TNFRSF17) Induces APRIL and BAFF Mediated Breast Cancer Cell Stemness

Recent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL (TNFSF13), and BAFF (TNFSF13B), which are type II membrane proteins, released in active forms by proteolytic cleavage and are primarily involved in B-lymphocyte maturation, have also been associated with tumor growth and aggressiveness in several solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition, migration, and stemness of breast cancer cells. Our findings show that both molecules increase epithelial to mesenchymal transition and migratory capacity of breast cancer cells, as well as cancer stem cell numbers, by increasing the expression of pluripotency genes such as ALDH1A1, KLF4, and NANOG. These effects are mediated by their common receptor BCMA (TNFRSF17) and the JNK signaling pathway. Interestingly, transcriptional data analysis from breast cancer cells and patients revealed that androgens can increase APRIL transcription and subsequently, in an autocrine/paracrine manner, enhance its pluripotency effect. In conclusion, our data suggest a possible role of APRIL and BAFF in breast cancer disease progression and provide evidence for a new possible mechanism of therapy resistance, that could be particularly relevant in aromatase inhibitors-treated patients, were local androgen is increased

Data_Sheet_1_BCMA (TNFRSF17) Induces APRIL and BAFF Mediated Breast Cancer Cell Stemness.docx

<p>Recent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL (TNFSF13), and BAFF (TNFSF13B), which are type II membrane proteins, released in active forms by proteolytic cleavage and are primarily involved in B-lymphocyte maturation, have also been associated with tumor growth and aggressiveness in several solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition, migration, and stemness of breast cancer cells. Our findings show that both molecules increase epithelial to mesenchymal transition and migratory capacity of breast cancer cells, as well as cancer stem cell numbers, by increasing the expression of pluripotency genes such as ALDH1A1, KLF4, and NANOG. These effects are mediated by their common receptor BCMA (TNFRSF17) and the JNK signaling pathway. Interestingly, transcriptional data analysis from breast cancer cells and patients revealed that androgens can increase APRIL transcription and subsequently, in an autocrine/paracrine manner, enhance its pluripotency effect. In conclusion, our data suggest a possible role of APRIL and BAFF in breast cancer disease progression and provide evidence for a new possible mechanism of therapy resistance, that could be particularly relevant in aromatase inhibitors-treated patients, were local androgen is increased.</p