Page 101 - TD-4-2

Tumor Discovery Cell-cell communication in cancer

disrupted by cells sending out erroneous signals, creating growth signals), tissue invasion and metastasis,
a self-serving microenvironment that evades normal cell- angiogenesis induction, and evasion of proliferative
to-cell cues. For example, if one cell has a mutation and restraints like apoptosis and senescence. These traits
3
no longer responds to signals from another adjacent cell, stem from dysregulated signaling pathways that normally
it can grow uncontrollably and form a tumor. Cell-to-cell regulate cell division, survival, and motility in healthy
communication plays a crucial role in tumor development tissues. Many experimental cancer therapies now focus on
and clonal evolution by enabling cancer cells to reprogram targeting these aberrant signaling molecules — key drivers
the surrounding tumor microenvironment (TME) and of oncogenic behavior.
immune cells. This communication supports processes Emerging research highlights that specialized cell-cell
4
essential for tumor development and spread, such as adhesion complexes, critical for maintaining epithelial
angiogenesis, immunoediting or immunosuppression, polarity and tissue structure, undergo dramatic remodeling
invasion, and multi-drug resistance. during epithelial-to-mesenchymal transition (EMT).
6
Cell-to-cell communication can occur through As EMT begins, these structures undergo disassembly,
membrane receptors and ligands or via soluble molecules dismantling cell-cell adhesion while redistributing or
like growth factors, cytokines, and chemokines. In addition, degrading junctional proteins. Among these, adherens
microRNAs and extracellular vesicles have recently been junctions act as central regulators, coordinating the integrity
5
identified as additional means of cell communication. of the entire junctional network—including tight junctions
Circulating nucleic acids are often deregulated in many and desmosomes. Cadherins, the transmembrane proteins
cancers and, as they affect all the disease’s hallmarks, they within adherens junctions, directly mediate intercellular
7
may serve as valuable biomarkers for cancers. Meanwhile, adhesion. Notably, E-cadherin—a hallmark of healthy
extracellular vesicles released from cancerous cells epithelial tissues—is frequently lost in metastatic cancers,
contribute to tumor growth and distribution. and experimental suppression of its function transforms
epithelial cells into invasive, motile populations. This shift
8
2. The community of cancer cells with their often coincides with upregulated N-cadherin expression, a
own language process termed cadherin switching, which is tightly linked
Two broad themes have emerged in recent years that have to tumor progression. 7
changed our perspective on cancer. First, cancer cells are The TME is a pathologically altered ecosystem that
not only communicating with their environment and each dynamically evolves during cancer progression, driven
other but also with normal cells in the body, such as cancer- by intricate cell-cell signaling networks. Integrating
9
associated fibroblasts or neurons. Second, cancer cells are multi-omics data offers a powerful lens to map tumor
not merely growing uncontrollably and ignoring their heterogeneity and decode the complex signaling pathways
surroundings; instead, they are strategically coordinating underlying these interactions. 10 Dec iphering the unique
actions among themselves as a community. molecular pathways driving tumor subtypes enables the
Unlike the relatively slow, soluble signals produced by discovery of novel therapeutic targets, paving the way for
ligands released from a cell towards a receptor over a short precision therapies tailored to each subtype’s molecular
11
distance, electrical pulses might offer a rapid and distant profile.
transmission system, similar to quorum sensing in bacteria 3. Drug-resistant tumor cells communicate
and electrical signals used by fungi. It is conceivable that directly with immune cells
similar quorum sensing systems exist in communities
of cancer cells, allowing them to communicate about Cancer cells are not only influencing healthy surrounding
nutrient locations and coordinate their metabolism. Once tissues with their communication tactics. There is growing
predictable classes of communication signals are identified, evidence that tumors can signal directly to non-cancer
we can start to see the building blocks of a code or language, cells within the TME. As cancer cells evolve, they acquire
where different patterns might be interpreted differently resistance to therapy by altering communication with non-
by various cells (Figure 1). Disrupting these signals could malignant cells in the TME (Figure 2). However, the specific
dysregulate the community, much like an army without its interactions between malignant and non-malignant cells
general. The challenge lies in understanding the language that cause this drug resistance remain largely unknown.
but not yet knowing the cellular response. Scientists have employed advanced single-cell RNA
As tumors progress, cancer cells acquire hallmark sequencing to determine the gene expression profile and
capabilities that enable unchecked malignancy. These an immune cell classifier to understand the immune
include autonomous growth (not triggered by external composition of the different tumor biopsy samples.
12

Volume 4 Issue 2 (2025) 93 doi: 10.36922/td.8323