Cancer Biology Commons^™

Her2 Amplification In Breast Cancer And Its Treatment Options, Emerald Cole, Zoe Grace Brigance

Student Scholar Symposium

Breast cancer affects approximately 2.3 million women worldwide, causing an estimated 670,000 deaths in 2022. Among its subtypes, 15-20% exhibit overexpression of Human Epidermal Growth Factor Receptor 2 (HER2), a tyrosine kinase receptor that drives tumor aggressiveness. HER2 activates the PI3K and RAS/RAF/MAPK pathways, promoting uncontrolled cell growth, proliferation, and survival. In HER2+ breast cancer, gene amplification leads to excess HER2 protein production, resulting in persistent signaling and unchecked tumor progression. However, this dependency on HER2 presents a key therapeutic opportunity. Trastuzumab, an anti-HER2 monoclonal antibody, inhibits HER2 signaling and enhances immune-mediated cancer cell destruction. When combined with Lapatinib, chemotherapy, …

Evaluating The Sna1 Gene Using Crispr Mediated Knockdown In Ewing Sarcoma Cells, Rosanna Jees, Sonia Cerrillo, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is a pediatric cancer with limited therapeutic options and poor long-term survival. CRISPR–Cas9–mediated gene editing provides a powerful tool for investigating tumor molecular behavior and identifying potential therapeutic targets. In this study, we worked with CRISPR–Cas9 in Ewing sarcoma ES8 cells to evaluate the roles of the transcription factors SNAI1 and SNAI2, both implicated in epithelial–mesenchymal transition and cancer progression. Using guide RNAs targeting each gene, we assessed proliferation, apoptosis, migration, and long-term survival through Incucyte live-cell imaging and colony-formation assays. Knockout of SNAI1 resulted in decreased cell proliferation and reduced migratory capacity compared with controls, suggesting a …

Effects Of Ptk2 Knockdown On Key Cellular Processes In Es8 Cells, Adrian Cruz, Emiliano Rueda, Dylan Andrews, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is an aggressive form of pediatric cancer characterized by rapid growth and metastatic potential, with limited treatment options available. PTK2 is a key regulator of many pathways involved in tumor behavior, including integrin-mediated adhesion, survival, and migration. This research lab investigated how CRISPR-Cas9 knockdown of PTK2 can affect cellular processes in ES8 Ewing sarcoma cells. To assess the effectiveness of reducing PTK2 expression, we utilized live-cell imaging, wound-healing assays, measurements of caspase activity, colony formation, and qRT-PCR. Our results showed that incomplete knockdown decreased cell proliferation and colony formation, while also increasing apoptotic activity. Additionally, migratory ability was …

How Cxcr4 Knockdown Affects Tumorigenic Properties In Es8 Cells, Gabriella Galdeano, Damon James, Terry Jo Shackleford

Mechanisms of Disease

C-X-C chemokine receptor type 4 (CXCR4) is a seven-transmembrane G-protein–coupled receptor (GPCR). When activated by its ligand SDF-1 (CXCL12), CXCR4 triggers signaling pathways that promote cell survival, proliferation, angiogenesis, and chemotaxis. Many cancers exploit the CXCR4/SDF-1 axis to support tumor growth and metastasis. Ewing sarcoma (ES8) is an aggressive pediatric bone and soft-tissue cancer, and elevated CXCR4 signaling has been linked to increased migration and metastatic behavior. ES8 cells, a well-established ES8 cell line, provided a model to study how CXCR4contributes to tumor progression. CRISPR-Cas9 genome editing was used to knock down CXCR4 in ES8 cells, delivered through lipid-based transfection. …

Investigating The Role Of Twist1 In Cancer Progression Using Crispr Knockdown, Abby Guerrero, Sofia Perez, Terry J. Shackleford

Mechanisms of Disease

TWIST1 is a transcription factor that plays a critical role in epithelial-mesenchymal transition (EMT), a process that promotes cancer cell migration, invasion, and metastasis. This study investigates the functional role of TWIST1 in cancer progression by using CRISPR/Cas9-mediated knockdown to examine its effects on apoptosis, proliferation, migration, and invasion. TWIST1 was knocked down in cancer cell lines using CRISPR/Cas9 assay. Knockdown efficiency and changes in genes were confirmed by qRT-PCR. Functional assays included caspase assays for apoptosis, MTT assays for proliferation, wound-healing assays for migration, Matrigel invasion assays, and colony formation assays to assess long-term growth and invasive potential. Across …

Itgb1 Knockdown Alters Apoptosis And Proliferation In Ewing Sarcoma Cells, Aditi Kumar, Magdalena Saad, Terry J. Shackleford

Mechanisms of Disease

Integrin beta 1 (ITGB1) is an adhesion receptor that link cells to the extracellular matrix and regulates pathways involved in survival, proliferation, and migration. In order to understand its role in Ewing Sarcoma, we applied CRISPR-Cas9 with two guide RNAs to knock down ITGB1 in ES8 cells. We then assessed changes in cell growth, death, movement, and gene expression using Incucyte live-cell imaging, colony formation assays, wound healing assays, and qRT-PCR. qRT-PCR showed partial ITGB1 reduction, with ITGB1_gRNA2 producing the strongest decrease. ITGB1_gRNA2 also led to a small increase in caspase activity and a 20-30% increase in proliferation at the …

Elucidating The Mechanism Of Neprilysin-Regulated Triple-Negative Breast Cancer Invasion, Kai Lam, Ellie Griner

Student Scholar Symposium

Triple-negative breast cancer (TNBC) is a highly invasive and difficult-to-target form of cancer. It is characterized by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor 2 receptors, making current targeted therapies ineffective and leaving chemotherapy as the primary treatment option. Previous studies in this lab have linked reduced expression of neprilysin (NEP), a membrane-bound protease that cleaves and inactivates mitogenic peptides, to a highly invasive phenotype in TNBC. Our data indicates that while NEP promotes phosphoinositol 3-kinase (PI3K) signaling, it simultaneously inhibits cellular invasion. Here, we begin to explain a possible mechanism behind the anti-invasive role …

Δ-Valerobetaine As A Novel Inhibitor Of Breast Cancer Cell Migration: Hinders Cellular Migration Of Mcf-7 Cells Through Reducing Atp Concentrations And Fak Activation, Braxton Ivie, Lincoln Brown, Bryson Lovorn

Student Scholar Symposium

δ-valerobetaine as a Novel Inhibitor of Breast Cancer Cell Migration: Hinders Cellular Migration of MCF-7 Cells Through Reducing ATP Concentrations and FAK Activation

Lincoln Brown, Braxton Ivie, Bryson Lovorn, Joshua Owens

Based on female breast cancer diagnoses from 2014-2020, the CDC reports that the 5-year relative survival rate for local and regional breast cancers was 98.9% and 86.3%, respectively, while the survival rate for metastasized cancers was reportedly 32.4%. These discrepancies in survival highlight an increased mortality rate when cancer metastasizes. Interestingly, aggressive tumors have been shown to metabolize fats at higher rates than low-metastatic tumors. Recently, our group has …

Host-Intrinsic Factors Determine Anti-Tumor Efficacy Of Exercise In Pancreatic Ductal Adenocarcinoma, Sumedha Pareek

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.

In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a …

A Ralgef Inhibitor Suppresses Lung Cancer Stem Cell Development And Tumorigenesis., Raphael Ngozichi Suarez Jigo

Electronic Theses and Dissertations

The RALGEF family of proteins are direct downstream effectors of the RAS oncoprotein. RALGEFs act as guanine nucleotide exchange factors (GEFs) for downstream RAL proteins, thus tying RAS to the regulation of RAL. Genetic studies have demonstrated RAL proteins to be key drivers of RAS-driven transformation and metastasis. Furthermore, this pathway has been implicated in chemoresistance, exocyst-mediated transport, and the modulation of cancer stem cells. Previous work in our lab reported the activity of a novel pan-RALGEF inhibitor (C4-180) against RAS-driven pancreatic cancer models. Here we show the agent to be active against in vitro and in vivo models of …

A Molecular Mechanism Of Epithelial To Mesenchymal Transition (Emt): An Evidence Based Lesson Applying Molecular Biology Through The Lens Of Cancer, Sophie Hasson, Melissa Rowland-Goldsmith

Open Educational Resources

This lesson aims to strengthen students’ critical thinking and molecular biology data analysis skills as well as their understanding of concepts related to the hallmark of cancer: tissue invasion and metastasis. Students begin by learning about the invasion of cancer cells, Epithelial-Mesenchymal Transition (EMT), and an important protein involved in EMT: E-cadherin. They then apply molecular biology knowledge to analyze data from multiple papers to infer the relationship between Snail and E-cadherin in different types of cancers. Next, they continue to interpret data from many papers to determine that a repressor transcription factor is present during EMT in cancer cells …

Mitochondria-Mediated Epigenetic Transfer Between Chondrosarcoma And Wild-Type Cells, Caleb C. J. Wyckoff

Biomedical Sciences Theses & Dissertations

Glioblastoma (GB), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), cholangiocarcinoma, and chondrosarcoma (CS) cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme exhibits transformation of alpha-ketoglutarate (αKG) into the oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers. Mitochondrial-mediated transfer between cancer cells and recipient cells is a significant event that impacts the physiology of the receiving cell, specifically the epigenetic landscape. Previous experiments indicating increased DNA methylation in mesenchymal stem cells exposed to IDH1 or IDH2 conditioned medium underscore the potential role of D2HG to alter methylation states. Additionally, the presence of …

Immunological Surveillance Against Cancer Across Mammals, Orsolya Vincze, Piotr Minias, Alexandre Corthay, Fernando Colchero, Jean-François Lemaître, Louise Maille, Tamás Malkócs, Justus Hagemann, Dalia A. Conde, Samuel Pavard, Antoine M. Dujon, Beata Ujvari, Frédéric Thomas, Amy M. Boddy, Carlo C. Maley, Damien Chevallier, Tuul Sepp, Thomas Pradeu, Mathieu Giraudeau

Presidential Fellows Articles and Research

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class …

Mathematical Model Of Ovarian Cancer Tumor Growth In Mice, Jessica A. Hoffman

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …

Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a decreased expression of genes related to replication and cell cycle. Moreover, deficiency in CDC6, an essential regulator of DNA replication, phenocopies SETDB1 inhibition. Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs …

Molecular Determinants Of Neoadjuvant Chemotherapy Resistance In Breast Cancer: An Analysis Of Gene Expression And Tumor Microenvironment, Hedda Michelle Guevara-Nieto, Carlos A. Orozco-Castaño, Rafael Parra-Medina, Jenny Nathaly Poveda-Garavito, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba Lucia Combita

School of Graduate Studies Faculty Publications

Neoadjuvant chemotherapy (NAC) is a critical component of breast cancer treatment, but the molecular mechanisms underlying resistance remain poorly understood. This study aimed to identify transcriptomic changes associated with NAC resistance across four breast cancer subtypes: Luminal A, Luminal B/HER2-positive, Luminal B/HER2-negative, and Triple-Negative Breast Cancer (TNBC). RNA-seq analysis was performed on paired pre- and post-NAC breast cancer samples from 32 nonresponders. Differentially expressed genes (DEGs) were identified, and functional enrichment analyses were conducted. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Tumor microenvironment (TME) infiltration was estimated using deconvolution algorithms. The results revealed distinct gene expression profiles …

Htlv-1 And Atll: Epidemiology, Oncogenesis, And Opportunities For Community-Informed Research In The United States, Adrian D. Altieri, Sean P. Reilly, Abu Mansalay, Alan Khoo, Nettie Johnson, Zafar K. Khan, Amy Leader, Pooja Jain, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-cells that is incurable in most patients and is associated with a median survival of less than 1 year. HTLV-1 also causes inflammatory disorders, including HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uveitis. The estimated lifetime risks of ATLL and HAM/TSP in HTLV-1 carriers are 3-5% and 0.25-1.8%, respectively. Although there is uncertainty about other health effects of HTLV-1, a recent meta-analysis showed an association between HTLV-1 and cardiovascular, cerebrovascular, and metabolic diseases and a 57% increased risk …

Swollen Lymph Node Metastasis In Gastric Cancer: A Forgotten Prognostic Signal In Need Of Clinical Action, Keykavous Parang, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Gastric cancer (GC) remains a leading cause of cancer mortality. While the extent of nodal involvement is a well-known prognostic factor, the specific entity of swollen lymph node metastasis (SLNM), bulky nodal tumor deposits detectable radiologically or pathologically, has received little attention in staging. Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC. Through robust data and rigorous propensity-matched analyses, SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis, even among patients undergoing curative resection. As precision oncology advances, the …

Inflammation And Detection: Rethinking The Biomarker Landscape In Gastric Cancer, Keykavous Parang, Koosha Paydary

Pharmacy Faculty Articles and Research

Gastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that …