The architect who never sleeps: Tumor‐induced plasticity

Abstract

Tumor cell plasticity is an event that has been observed in several malignancies. In fact, most of the solid tumors are characterized by cellular heterogeneity and undergo constant changes as the tumor develops. The increased plasticity displayed by these cells allows them to acquire additional properties, enabling epithelial-mesenchymal transitions, dedifferentiation and the acquisition of stem cell-like properties. Here we discuss the particular importance of an inflammatory microenvironment for the bidirectional control of cellular plasticity and the potential for therapeutic intervention.

The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration

“…Our data develop these findings, suggesting that NFKB-mediated SASP exposure might contribute to plasticity during tumor formation through dedifferentiation and amplification of the stem cell of origin, as has been demonstrated previously in colon cancer models (Myant et al 2013;Schwitalla et al 2013). In addition, SASP effects could result in an expansion of stem cell numbers, thereby increasing the likelihood that these cells could acquire mutations or favor the induction of cells to reside in a more plastic undefined state that might be more susceptible to transformation (Tschaharganeh et al 2014;Varga et al 2014). This could help explain how senescence can favor tumor formation during aging, and it will be interesting to determine whether age-associated in vivo senescence has similar effects on plasticity induction.…”

Genetics and metabolic deregulation following cancer initiation: A world to explore

“…In last decades, novel diagnostic methods and therapies have been implemented related to cancer [40]. However, despite these advances, the number of patients that succumb has increased globally [40].…”

“…However, despite these advances, the number of patients that succumb has increased globally [40]. One of the reasons is the chemotherapeutic resistance developed by cancer cells [4,40].…”

The Molecular Connections between Lung and Pancreatic Cancer Metastases: are we not seeing the Forest for the Trees?

“…Reduction of O 2 levels in tumors occurs by heterogenic tumor proliferation [248,249]. Hypoxia is a kind of signaling pathway that prompts HIF-1 to induce stromal mesenchymal cells to secrete lysyl oxidase (LOX), which signals tumor cells to undergo dedifferentiation to CSCs, and mediates bone marrow progenitor cell recruitment at premetastatic niches for metastasis [137,221,247,250,251]. Detached tumor cells likely divert from this program when there is no premetastatic niche conducive for survival [138,252].…”

“…Genetic background across the tumor-stromal axis is the blueprint for cancer behavior [219,251,292]. Inquiries might include: pleiotropic pathways, genomic reconfigurations (e.g., aneuploidy, copy number variations, microinsertions, microdeletions, and translocations), genetic mutations (e.g., promoter, intronic, exonic, and splicing mutations), epigenetic alterations (e.g., de-, hyper-, and hypo-methylation, and deacetylation), epistatic genes and their interactions, diversified miR expression, EMT and non-EMT drivers of tumor invasion, autophagy and metabolism, ECM interactions, exosome-content dispersion, inflammatory mediators, stromal and ECM mediators, and angiogenic and lymphangiogenic mediators.…”