Biology subjects

Wailemann, R. A. M.

Publications and source records attributed to Wailemann, R. A. M..

4 recordsLinked to original sources

bioRxiv2026

A comprehensive temporal proteome and phosphoproteome dataset of Y1 adrenocortical cells under FGF2 stimulation and SOS inhibition

The Y1 mouse adrenocortical tumor cell line is a classic model for cancer studies and ACTH mediated steroidogenesis. The KRAS gene amplification and SOS mediated activation sustain elevated ERK levels, which drive the tumor phenotype of this cell line. In addition, the mitogen FGF2 induces atypical cytotoxic stress and consequent cell death rather than proliferation in this system, imposing a strong perturbation on KRAS ERK signaling dynamics. Recent research from our group revealed that SOS is not solely responsible for KRAS activation in the Y1 cells, indicating a more complex regulatory landscape of GEFs and GAPs. This motivated the generation of a comprehensive time resolved proteome (DIA) and TMT phosphoproteome (DDA) in a 0 to 30 minute time course under FGF2 stimulation or combined with SOS inhibitor, with the presence or absence of FBS stimulation, in technical triplicate using Q Exactive and Thermo Lumos mass spectrometers, respectively. This dataset can enable latent mechanisms between the life and death switch caused by FGF2 signaling and the alternate stress response caused by impaired SOS dependent activation. This analysis yielded 14,512 phosphosites and 8,919 protein groups, where 10,471 phosphosites and 111 protein groups showed differential abundance with statistical significance (limma, FDR < 0.05%). This dataset provides a versatile resource for downstream applications, which includes dynamic modeling such as ordinary differential equation based frameworks, for which temporal datasets remain scarce. The data contained in this preprint will be available on JPOST Repo after the publication.

cancer biology↗

bioRxiv2025

RASGRP4 is a key factor in KRAS activation mediated by SOS in Y1 mouse tumor cell line

The Y1 mouse adrenocortical carcinoma cell line presents amplification of the KRas oncogene and high-basal levels of KRAS-GTP mediated by the GEF SOS. In this research, we developed a dynamic model based on ordinary differential equations of the KRAS-GTP activation mediated by SOS in Y1 cells, which showed that SOS only is not sufficient to reach the high-basal levels of KRAS-GTP experimentally observed for this cell line. Interestingly, a modification in this system, which added another GEF in the model, made the model reach the expected levels of KRAS activation, leading to the hypothesis that there was a missing element in this system. To find this missing element, a PCR panel of RasGEFs was performed and the GEF Rasgrp4 was found highly expressed in parental Y1 cell lines, indicating that this was the missing element in the system. Finally, tumor growth assays in Balb/c-NUDE mice with the Y1 cell versus RASGRP4 CRISPR depleted Y1 cells, showed reduced tumor growth and frequency for the RASGRP4 depleted cells.

systems biology↗

bioRxiv2023

Paradoxical activation of oncogenic signaling as a cancer treatment strategy

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.

cancer biology↗

bioRxiv2020

Distinct photooxidation-induced cell death pathways lead to selective killing of human breast cancer cells

Lack of effective treatments for aggressive breast cancer is still a major global health problem. We previously reported that Photodynamic Therapy using Methylene Blue as photosensitizer (MB-PDT) massively kills metastatic human breast cancer, marginally affecting healthy cells. In this study we aimed to unveil the molecular mechanisms behind MB-PDT effectiveness. Through lipidomic and biochemical approaches we demonstrated that MB-PDT efficiency and specificity relies on polyunsaturated fatty acids-enriched membranes and on the better capacity to deal with photooxidative damage displayed by non-tumorigenic cells. We found out that, in tumorigenic cells, lysosome membrane permeabilization is accompanied by ferroptosis and/or necroptosis. Our results broadened the understanding of MB-PDT-induced photooxidation mechanisms and specificity in breast cancer cells. Therefore, we demonstrated that efficient approaches could be designed on the basis of lipid composition and metabolic features for hard-to-treat cancers. The results further reinforce MB-PDT as a therapeutic strategy for highly aggressive human breast cancer cells.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗