The value of desmosomal plaque-related markers to distinguish squamous cell carcinoma and adenocarcinoma of the lung

An antibody panel is needed to definitively differentiate between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in order to meet more stringent requirements for the histologic classification of lung cancers. Staining of desmosomal plaque-related proteins may be useful in the diagnosis of lung SCC. The specificity for SCC of membrane staining for PKP1, KRT15, and DSG3 was 97.4%, 94.6%, and 100%, respectively, and it was 100% when the markers were used together and in combination with the conventional markers (AUCs of 0.7619 for Panel 1 SCC, 0.7375 for Panel 2 SCC, 0.8552 for Panel 1 AC, and 0.8088 for Panel 2 AC). In a stepwise multivariate logistic regression model, the combination of CK5/6, p63, and PKP1 in membrane was the optimal panel to differentiate between SCC and AC, with a percentage correct classification of 96.2% overall (94.6% of ACs and 97.6% of SCCs). PKP1 and DSG3 are related to the prognosis. PKP1, KRT15, and DSG3 are highly specific for SCC, but they were more useful to differentiate between SCC and AC when used together and in combination with conventional markers. PKP1 and DSG3 expressions may have prognostic value.MEFV was supported by PAIDI programme, Group BIO309, Junta de Andalucía

PKP1 and MYC create a feedforward loop linking transcription and translation in squamous cell lung cancer

[Purpose] Plakophilin 1 (PKP1) is well-known as an important component of the desmosome, a cell structure specialized in spot-like cell-to-cell adhesion. Although desmosomes have generally been associated with tumor suppressor functions, we recently found that PKP1 is recurrently overexpressed in squamous cell lung cancer (SqCLC) to exert an oncogenic role by enhancing the translation of MYC (c-Myc), a major oncogene. In this study, we aim to further characterize the functional relationship between PKP1 and MYC.[Methods] To determine the functional relationship between PKP1 and MYC, we performed correlation analyses between PKP1 and MYC mRNA expression levels, gain/loss of function models, chromatin immunoprecipitation (ChIP) and promoter mutagenesis followed by luciferase assays.[Results] We found a significant correlation between the mRNA levels of MYC and PKP1 in SqCLC primary tumor samples. In addition, we found that MYC is a direct transcription factor of PKP1 and binds to specific sequences within its promoter. In agreement with this, we found that MYC knockdown reduced PKP1 protein expression in different SqCLC models, which may explain the PKP1-MYC correlation that we found. Conversely, we found that PKP1 knockdown reduced MYC protein expression, while PKP1 overexpression enhanced MYC expression in these models.[Conclusions] Based on these results, we propose a feedforward functional relationship in which PKP1 enhances MYC translation in conjunction with the translation initiation complex by binding to the 5’-UTR of MYC mRNA, whereas MYC promotes PKP1 transcription by binding to its promoter. These results suggest that PKP1 may serve as a therapeutic target for SqCLC.The CTS-993 group is funded by the Ministry of Economy of Spain (SAF2015-67919-R), the Junta de Andalucía (Pl-0245-2017, PIGE-0440-2019, PI-0135-2020, PIGE-0213-2020, P20-00688), the Plan propio de la Universidad de Granada (PPJIA2019-06, and B‐CTS‐126‐UGR18), an International Association for the Study of Lung Cancer (IASLC) Young Investigator Award 2017, and the Spanish Association for Cancer Research (LAB-AECC-2018). L.B, J.M-P, and D.J.G. were supported by a “Fundación Benéfica Anticáncer Santa Cándida y San Francisco Javier” predoctoral fellowship. L.B. is currently funded by the Ministry of Health and Social Welfare of Junta de Andalucía (RH-0051-2020). J.C.A.-P is a Marie Curie Postdoctoral Researcher (European Commission. H2020-MSCA-IF-2018 #837897). P.P. was supported by a PhD “La Caixa Foundation” LCF/BQ/DE15/10360019 Fellowship. A.A, A.M.A. and F.R-S were supported by a Spanish Ministry of Education, Culture and Sports FPU fellowship: FPU17/00067, FPU17/01258, and FPU19/05124.Peer reviewe

Innovación docente para convencidos : VI Jornadas de Innovación Educativa de la Universidad de La Laguna

Las VI Jornadas de Innovación Educativa representan la continuidad del esfuerzo de la Universidad de La Laguna en su apuesta por la Innovación en el ámbito de la docencia. El profesorado actual debe formarse en los distintos procesos de diseño, puesta en práctica, evaluación y reflexión necesarios para el desempeño docente, así como adquirir competencias pedagógicas diferentes, adaptadas al entorno social y a un alumnado que demanda nuevos modelos de aprendizaje en la universidad. Esta edición de las Jornadas de Innovación se ha centrado en la idea del docente como un profesional convencido y reflexivo, que conoce y valora la importancia de la innovación en la docencia universitaria como medio para alcanzar unos fines que van más allá de transmitir el conocimiento de un repertorio técnico, por más denso y extenso que éste pueda ser, despreciando la posibilidad de enseñar a preguntar más que a responder. La mejora de la calidad educativa está directamente vinculada a un profesorado que aspira a convertirse en un especialista en enfrentarse a situaciones problemáticas de distinta naturaleza, a través de una actividad reflexiva que no se agota en la búsqueda de los medios idóneos para unos fines ya definidos, sino que trasciende hasta la indagación sobre los propios fines