Miranda, M. S. | bioRxiv Science

bioRxiv2021

A short ERK5 isoform modulates nucleocytoplasmic shuttling of active ERK5 and associates with poor survival in breast cancer

BackgroundThe nucleocytoplasmic shuttling of ERK5 has gained recent attention as a regulator of its diverse roles in cancer progression but the exact mechanisms for this shuttling are still under investigation. MethodsUsing in vitro, in vivo and in silico studies, we investigated the roles of shorter ERK5 isoforms in regulating the nucleocytoplasmic shuttling of active phosphorylated-ERK5 (pERK5). Retrospective cohorts of primary and metastatic breast cancer cases were used to evaluate the association of the subcellular localization of pERK5 with clinicopathological features. ResultsExtranuclear localization of pERK5 was observed during cell migration in vitro and at the invasive fronts of metastatic tumors in vivo. The nuclear and extranuclear cell fractions contained different isoforms of pERK5, which are encoded by splice variants expressed in breast and other cancers in the TCGA data. One isoform, isoform-3, lacks the C-terminal transcriptional domain and the nuclear localization signal. The co-expression of isoform-3 and full-length ERK5 associated with high epithelial-to-mesenchymal transition (EMT) and poor patient survival. Experimentally, expressing isoform-3 with full-length ERK5 in breast cancer cells increased cell migration, drove EMT and led to tamoxifen resistance. In breast cancer patient samples, pERK5 showed variable subcellular localizations where its extranuclear localization associated with aggressive clinicopathological features, metastasis, and poor survival. ConclusionOur studies support a model of ERK5 nucleocytoplasmic shuttling driven by splice variants in an interplay between mesenchymal and epithelial states during metastasis. Using ERK5 as a biomarker and a therapeutic target should account for its splicing and context-dependent biological functions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/436061v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@1491ed5org.highwire.dtl.DTLVardef@1875fbeorg.highwire.dtl.DTLVardef@9edbbcorg.highwire.dtl.DTLVardef@16c34c8_HPS_FORMAT_FIGEXP M_FIG C_FIG ERK5 isoform-3 expression deploys active ERK5 (pERK5) outside the nucleus to facilitate EMT and cell migration. In cells dominantly expressing isoform-1, pERK5 shuttles to the nucleus to drive cell expansion.

cancer biology↗

bioRxiv2020

Integrative taxonomy reveals hidden species within the western Atlantic Callichirus major s. l. (Decapoda, Axiidea, Callichiridae)

The ghost shrimp Callichirus major (Say, 1818) is widely distributed in the Atlantic Ocean from [~]23{degrees}N to [~]26{degrees}S, and has also been reported from the tropical eastern Pacific. Evidence has been accumulating over many years that C. major is actually a species complex. Yet, the name C. major is widely and frequently used in many kinds of research. The current lack of clarity in the use of the name C. major has resulted in nomenclatural instability, but also in unreliability and miscommunication of the available ecological and distributional information. Existing morphological and molecular evidence is reviewed and new evidence presented for the specimens from the southern localities previously assigned to C. major s. l. actually being a new species. That new species is herein described based on morphological and molecular evidence. Additionally, a neotype is selected for C. major in order to settle the defining characters of C. major s. str. and, therefore, ensuring the correct use of this name.

zoology↗