Vimentin is required for tumor progression and metastasis in a mouse model of non-small cell lung cancer.

Vimentin is highly expressed in metastatic cancers, and its expression correlates with poor patient prognoses. However, no causal in vivo studies linking vimentin and non-small cell lung cancer (NSCLC) progression existed until now. We use three complementary in vivo models to show that vimentin is required for the progression of NSCLC. First, we crossed LSL-KrasG12D; Tp53fl/fl mice (KPV+/+) with vimentin knockout mice (KPV-/-) to demonstrate that KPV-/- mice have attenuated tumor growth and improved survival compared with KPV+/+ mice. Next, we therapeutically treated KPV+/+ mice with withaferin A (WFA), an agent that disrupts vimentin intermediate filaments (IFs). We show that WFA suppresses tumor growth and reduces tumor burden in the lung. Finally, luciferase-expressing KPV+/+, KPV-/-, or KPVY117L cells were implanted into the flanks of athymic mice to track cancer metastasis to the lung. In KPVY117L cells, vimentin forms oligomers called unit-length filaments but cannot assemble into mature vimentin IFs. KPV-/- and KPVY117L cells fail to metastasize, suggesting that cell-autonomous metastasis requires mature vimentin IFs. Integrative metabolomic and transcriptomic analysis reveals that KPV-/- cells upregulate genes associated with ferroptosis, an iron-dependent form of regulated cell death. KPV-/- cells have reduced glutathione peroxidase 4 (GPX4) levels, resulting in the accumulation of toxic lipid peroxides and increased ferroptosis. Together, our results demonstrate that vimentin is required for rapid tumor growth, metastasis, and protection from ferroptosis in NSCLC.

Pivoting to a Remote-Learning Summer Student Program during the COVID-19 Pandemic.

Research experience garnered through summer student programs (SSPs) is critical for high school and college student retention in science, technology, engineering, and math (STEM) disciplines. However, the global coronavirus disease (COVID-19) pandemic prevented in-person SSPs in 2020, eliminating these essential experiences that students need to advance their STEM training. In response, we created a remote-learning model that can be broadly adapted for other SSPs. We aimed to uphold our traditional SSP's academic rigor by cultivating critical thinking skills, providing mentorship, and equipping students with tools to serve as public health ambassadors in their communities. We designed the remote SSP around an anchor topic to integrate didactic lectures with research-based independent projects. Program success was evaluated quantitatively and qualitatively via content assessments and written feedback. By comparing preassessments to postassessments, we show that students gained general scientific literacy and improved critical thinking skills. Based on qualitative measures, students were satisfied with their mentorship, reported that they would use what they learned through the SSP in the future, indicated that they had the tools to understand and communicate public health information, and, overall, rated the quality of the SSP positively. As the pandemic continues to necessitate remote learning, traditional in-person experiences will need to be adapted to best support students. We have developed a modular and adaptable SSP that upholds the same standards as the traditional SSP by continuing to provide essential experiences necessary to advance students' training in STEM.