Cell Migration–Proliferation Dichotomy in Cancer: Biological Fact or Experimental Artefact?

Simple Summary: Migration–proliferation dichotomy (MPD) is a characteristic that has been observed in cancer cells growing in artificial culture media. The MPD principle states that when cells begin to grow in number (cell proliferation), their ability to migrate from one point to another (cell migration) is paused, and vice versa. This phenomenon has been used to study cancer advancement in cancer cells growing in culture, and is proposed to be responsible for the adverse therapeutic outcomes observed in patients with cancer. However, MPD has not been comprehensively investigated in cancer tissues obtained directly from patients. This study investigated MPD in stomach and bowel cancers using gene expression signatures of natural cancers. The overall findings confirm that cell proliferation and migration occur in the reverse direction in cancer cells, which is in keeping with the features that have long been observed in artificially grown cancer cells. These results also provide a basis for further investigation of MPD in natural cancers. The migration–proliferation dichotomy (MPD) has long been observed in cultured cancer cells. This phenomenon is not only relevant to tumour progression but may also have therapeutic significance in clinical cancer. However, MPD has rarely been investigated in primary cancer. This study aimed to either confirm or disprove the existence of MPD in primary cancer. Using primary gastric, colorectal and prostate cancer (GC, CRC and PCa) cohorts from the Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center, this study interrogated the MPD phenomenon by utilising RNA–Seq-based proliferation (CIN70 signature) and migration (epithelial-mesenchymal transition) indices, as well as gene set enrichment analyses (GSEA). Alternative hypothetical migration–proliferation models—The simultaneous migration–proliferation (SMP) and phenotype–refractory (PR) models—were compared to the MPD model by probing the migration–proliferation relationships within cancer stages and between early- and late-stage diseases using chi-square and independent T tests, z-score statistics and GSEA. The results revealed an inverse relationship between migration and proliferation signatures overall in the GC, CRC and PCa cohorts, as well as in early- and late-stage diseases. Additionally, a shift in proliferation- to migration dominance was observed from early- to late-stage diseases in the GC and CRC cohorts but not in the PCa cohorts, which showed enhanced proliferation dominance in metastatic tumours compared to primary cancers. The above features exhibited by the cancer cohorts are in keeping with the MPD model of the migration–proliferation relationship at the cellular level and exclude the SMP and PR migration–proliferation models. [ABSTRACT FROM AUTHOR]