Migration rather than proliferation transcriptomic signatures are strongly associated with breast cancer patient survival

Abstract

The efficacy of prospective cancer treatments is routinely estimated by in vitro cell-line proliferation screens. However, it is unclear whether tumor aggressiveness and patient survival are influenced more by the proliferative or the migratory properties of cancer cells. To address this question, we experimentally measured proliferation and migration phenotypes across more than 40 breast cancer cell-lines. Based on the latter, we built and validated individual predictors of breast cancer proliferation and migration levels from the cells’ transcriptomics. We then apply these predictors to estimate the proliferation and migration levels of more than 1000 TCGA breast cancer tumors. Reassuringly, both estimates increase with tumor’s aggressiveness, as qualified by its stage, grade, and subtype. However, predicted tumor migration levels are significantly more strongly associated with patient survival than the proliferation levels. We confirmed these findings by conducting siRNA knock-down experiments on the highly migratory MDA-MB-231 cell lines and deriving gene knock-down based proliferation and migration signatures. We show that cytoskeletal drugs might be more beneficial in patients with high predicted migration levels. Taken together, these results testify to the importance of migration levels in determining patient survival.

Cysteine and Folate Metabolism Are Targetable Vulnerabilities of Metastatic Colorectal Cancer

“…Remarkably, wound healing assays indicated that the primary cell line SW480 had a higher migratory capacity than the metastatic cell lines ( Figure 1 f and Figure S1g ), consistent with the fact that proliferation and migration gene expression programs have been reported to be different [ 17 ]. Examining markers of epithelial mesenchymal transition (EMT), we found that SW480 displayed reduced E-cadherin ( Figure 1 g and Figure S1h ) and increased EMT transcription factor ZEB1/2 ( Figure 1 g and Figure S1i ).…”

HERC1 Regulates Breast Cancer Cells Migration and Invasion

“…Cell migration and invasion are critical steps in the metastatic dissemination of tumor cells, a process that constitutes the principal cause of death due to solid tumors [ 1 ]. In fact, it has been reported that the regulation of transcriptional pathways related to migration, rather than proliferation, are strongly associated with breast cancer patient’s survival [ 28 ], highlighting the importance of its modulation in the development of new treatments for the clinical management of this disease.…”

The Emerging Roles of Heterochromatin in Cell Migration

“…Unfortunately, a first-order link between heterochromatin and cancer does not always exist. In recent years it has become apparent that cancer cell proliferation and migration may be supported by different transcriptional plans (Nair et al, 2019;Luo et al, 2020) as well as by different global chromatin organization features; in melanoma it seems that euchromatin supports better cell proliferation, whereas increased chromatin condensation (heterochromatin levels) better supports cell migration (Barsotti et al, 2015;Maizels et al, 2017). Thus, targeting cancer cells by a single epigenetic drug might be challenging.…”