Biology subjects

Gatie, M. I.

Publications and source records attributed to Gatie, M. I..

3 recordsLinked to original sources

bioRxiv2025

L1CAM signaling through planar cell polarity generates SOX2+ metastatic progenitors in lung adenocarcinoma

Plasticity transitions during carcinoma progression generate fetal-like progenitor states with metastatic capacity. How these progenitors emerge and persist during tumor progression remains unknown. Here, we elucidate a process that drives the emergence of SOX2+ metastatic progenitors in lung adenocarcinomas (LUAD). LUAD cells in the tumor invasive front and distant metastases express the cell adhesion molecule L1CAM, a marker of regenerative epithelial progenitors and a mediator of cell-basement membrane and cell-cell interactions. L1CAM-mediated adhesion to perivascular basement membrane is known to stimulate the proliferation of extravasated micrometastatic cells. We now identify a distinct and broader role of L1CAM as promoter of the SOX2+ LUAD progenitor state. We show that L1CAM at cell-cell interfaces promotes the assembly of the planar cell polarity (PCP) complex in metastatic LUAD progenitors. L1CAM-dependent PCP acting through a non-canonical WNT signaling activates c-Jun, which cooperates with the chromatin remodeling factor CHD1 to drive SOX2 expression and metastatic activity. This axis sustains the tumor-initiating and regenerative capacity of LUAD progenitor cells. By illuminating the role of L1CAM and PCP signaling in the generation of SOX2+ LUAD progenitors, our findings identify potential new targets to treat metastatic cancer.

cancer biology↗

bioRxiv2020

Lactate Accelerates Mouse ES Cell Differentiation Towards the XEN Lineage

Metabolism plays a crucial role for cell survival and function; however, recent evidence has implicated it in regulating embryonic development. The inner cell mass undergoes orchestrated cellular divisions resulting in the formation of embryonic stem cells and extraembryonic endoderm (XEN) cells. Concomitantly, changes in the metabolic profile occurs during development and are well-documented in the embryonic lineages. However, a comprehensive multi-omics analysis of these features in XEN cells remains lacking. We observed that feeder-free XEN cells exhibited high sensitivity to glycolytic inhibition in addition to maintaining elevated intra- and extracellular lactate levels. XEN cells maintain high lactate levels by increased LDHA activity and re-routing pyruvate away from the mitochondria. Importantly, exogenous lactate supplementation or promoting intracellular lactate accumulation enhances XEN differentiation in vitro. Our results highlight how lactate contributes to XEN differentiation in the mammalian embryo and may serve to enhance reprogramming efficiency of cells used for regenerative medicine. HighlightsO_LIFeeder-free XEN cells exhibit high sensitivity to glycolytic inhibition C_LIO_LIDistinct transcriptomic, proteomic and metabolomic profile exists between feeder-free ES and XEN cells C_LIO_LIElevated intracellular and extracellular lactate is observed in feeder-free XEN cells C_LIO_LILactate enhances feeder-free XEN differentiation in vitro C_LI

developmental biology↗

bioRxiv2018

Serum-dependent and independent regulation of PARP2

PARP2 belongs to a family of proteins involved in cell differentiation, DNA damage repair, cellular energy expenditure, chromatin modeling and cell differentiation. In addition to these overlapping functions with PARP1, PARP2 participates in spermatogenesis, T-cell maturation, extraembryonic endoderm formation and adipogenesis. The function(s) of PARP2 is far from complete, and the mechanism(s) by which the gene and protein are regulated are unknown. In this study, we found that two different mechanisms are used in vitro to regulate PARP2 levels. In the presence of serum, PARP2 is degraded through the ubiquitin-proteasome pathway, however, when serum is removed, PARP2 is rapidly sequestered into an SDS- and urea-insoluble fraction. This sequestration is relieved by serum in a dose-dependent manner, and again PARP2 is detected by immunoblotting. Furthermore, and despite the presence of a putative serum response element in the PARP2 gene, transcription is not affected by serum deprivation. These observations that PARP2 is tightly regulated by distinct pathways highlights the critical roles PARP2 plays under different physiological conditions.

cell biology↗