Table 2.

TPM isoform usage in urothelial bladder carcinogenesis. EMT: epithelial–mesenchymal transition.

Bladder Cancer Stage	Hallmark	Process	TPM Involvement
Normal	Self-sufficiency in growth signals	Normal expression levels of TPM genes	Tpm 1.6 and Tpm 1.7—formation of stress fibres, cell stability, reduced motility
Suppression	Insensitivity to growth inhibitory signals	Cell-cycle arrest in G0/G1 if proliferating too much TPM1 + MEG3 causes apoptosis by upregulation of Bcl2 and caspase3	TPM1—acts as tumour suppressor
Initiation	Evasion of programmed cell death	Decreased expression of TPM1 and TPM2 TPM1 is downregulated due to increased micro-RNA 96 (suppression lost)	Loss of TPM1—EMT Tpm 2.1—responsible for anoikis, maintains cell–cell adhesion
Non-invasive	Limitless replicative potential	Mutagenic MAPK signalling activated	Tpm3.1—cellular growth, proliferation and motility
Invasive	Sustained angiogenesis	Invasion into extracellular matrix (ECM) Angiogenesis stimulated by concurrent pathways	LMW TPMs—formation of lamellipodia, increased cell motility and morphogenesis
Metastasis	Tissue invasion and death	Breakthrough ECM with distant spread	LMW isoforms of TPM3 and TPM4—Cancer cell survival, focal adhesion, MEK/ERK-mediated proliferation
	Evading immune destruction	Ectopic expression of TPM1 and TPM2 Continued uninhibited anchorage-independent growth