For more than two decades, cancer researcher Lynne-Marie Postovit has investigated cancer cell plasticity to elucidate the molecular alterations that enable cells to adapt to their microenvironment.
Image credit:BRIAN HILLER, Lynne-Marie Postivot, Modified by Erin Lemieux
The dynamic interplay between cancer cells and their surrounding tumor microenvironment (TME) has long captivated Lynne-Marie Postovit, a researcher at Queen’s University, for over two decades. Understanding this interaction has become a central focus of her scientific work.
In 2012, when The Scientist interviewed her, Postovit was a principal investigator at the University of Western Ontario, investigating how developmental-stage molecules influence cancer cell aggressiveness,1,2 and began exploring how low‑oxygen stress affects the expression of these embryonic signals.
Marking the 40th anniversary of The Scientist, we reconnect with Postovit to review the trajectory of her cancer research. Since our previous interview, she has continued to examine hypoxia’s impact on cancer cells and the TME, and expanded her investigations to include how TME disruptions drive transcriptomic and epigenomic alterations that affect cell plasticity, with the aim of clarifying the networks that govern cancer progression.
The Tumor Microenvironment: A Shaper of Cells
Postovit’s fascination with how alterations in the tumor microenvironment influence cancer progression originated during her graduate studies under biologist Charles Graham at Queen’s University, where she concentrated on hypoxia—a factor linked to treatment resistance, tumor growth, and metastasis.3 “Hypoxia is a pervasive and powerful stressor within the tumor microenvironment,” Postovit noted. “It has been demonstrated that stresses such as hypoxia strongly promote plasticity and heterogeneity in cancers.”
From Single Molecules to Networks
Although Postovit’s early research centered on individual molecules and the influence of TME perturbations on their effects in cancer cells, she now adopts a broader perspective, examining simultaneous alterations across multiple genes and molecules.
“We are keenly interested in networks, which is challenging because a perturbation reveals effects across the entire network rather than a single gene,” she explained. “It is complex but exciting.”
Postovit attributes the rise of high‑throughput methods—such as RNA sequencing and proteomic analysis—as pivotal to the evolution of her research. “These technologies have transformed what we can accomplish,” she said. “When I began as a graduate student, we lacked a reference human genome, cell‑editing capabilities, and advanced sequencing; gene arrays were considered a major advance. I could not have foreseen the possibilities that would emerge.”
A recent study by Postovit and her team illustrated how network‑centric analyses can uncover global alterations that drive cancer cell plasticity under hypoxia. Examining the transcriptome, epigenome, and translatome—representing actively translated mRNAs—they found that low oxygen reprograms breast cancer cells, prompting many genes to alter their transcription start sites and affecting protein production efficiency.8 This epigenetic shift mirrors changes seen in embryonic stem cells, indicating a general stress‑response mechanism for modulating protein synthesis.
Presently, Postovit employs comparable high‑throughput approaches to investigate global changes in other women’s cancers. For example, she is leading a project on dedifferentiated endometrial cancer, an uncommon but highly aggressive disease, where her team analyzes single‑cell alterations that contribute to tumor heterogeneity.
Throughout her career, Postovit has let the data guide her research, even when it required pursuing challenging avenues. “Engaging with interesting, often difficult, material is essential,” she said. “Taking an easy route may boost productivity, but it will not meaningfully advance the field or alter our perspectives.”
