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J. Martin-Padron



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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-010 - Oncogenic Role of PKP1 in Non-Small-Cell Lung Cancer. (ID 8635)

      09:30 - 16:00  |  Author(s): J. Martin-Padron

      • Abstract

      Background:
      Non-Small-Cell Lung Cancer (NSCLC) is often diagnosed at an advanced stage and carries a poor prognosis. Greater knowledge of the molecular origins and progression of lung cancer may lead to improvements in the treatment and prevention of the disease. Although it is well-known the importance of desmosomes in cell-to cell adhesion, several evidences suggest that some of their structural proteins may have additional and relevant roles in cancer development. In this regard, Plakophilin 1 (PKP1) is up-regulated in primary NSCLC tumors (SCC and AD) suggesting an oncogenic role in tumor development that it is probably beyond their role into cell-to-cell adhesion.

      Method:
      In order to gain greater insight into the multifuntional role of PKP1 in NSCLC tumours, we have generated functional models in that express different levels of PKP1 protein using siRNA, Crispr Cas9 system or lentivirus-vectors. We have carried out several phenotypical assays to demonstrate the PKP1´s role in tumor development into NSCLC cell lines (proliferation, cell cycle, apoptosis, wound healing, BrdU and colony assays, etc.) and an in vivo xenograph assays using CrispR-Cas9.

      Result:
      On the one hand, when we inhibit PKP1 in cell lines with high PKP1 protein basal level, we observe an increment in migration in the wound-healing assays. This PKP1-function formally can be considered a tumour-suppressor activity. On the other hand, we have also observed pro-oncogenic activity after PKP1 expression inhibition. In this way, after the knock-down or knock-out PKP1, we have observed cell-growth and cell-cycle arrest and higher levels of apoptosis. Additonally, when we over-express PKP1 in a cell line with no PKP1 protein basal level,we detect cell growth and S phase increment, and apoptosis reduction; gainning new evidences that support pro-oncogenic role of this protein. To determine the results of these apparently opposing tumoral activity, we have developed and in vivo xenograph assay using CrispR-Cas9. The tumoral burden dynamics in the model clearly indicate that, although the loss of PKP1 promotes cell-migration, overall the role of PKP1 is pro-oncogenic. Currently, we are performing a PKP1 immunoprecipitation and an expression array in order to elucidate PKP1 tumoral functions that could help us to explain these new pro-oncogenic activities that remain unknown.

      Conclusion:
      In conclusion, our results indicate PKP1 protein has a contribution in NSCLC development and it may be a potential useful for NSCLC diagnosis, prognosis and treatment.