| Abstract: |
Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occurs in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA polymerase I subunit A (POLR1A). Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest on CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5− tumor cells. Therefore, a common architecture in CRCs is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins. © 2020 Elsevier Inc. Morral and colleagues discovered that most rRNA and proteins synthesized in colorectal cancers (CRCs) are contributed by a limited subset of tumor cells that reside adjacent to the stroma. This architecture defines a common stem cell hierarchy. In some CRCs, the biosynthetic tumor cell population renders LGR5+ tumor cells dispensable. © 2020 Elsevier Inc. |
