Table 1.

TRPM2 Function in Human Cancer

Cancer Type	Study System	Activity	Mechanism	References
Breast Cancer	Breast adenocarcinoma cell lines	TRPM2 inhibition reduced cell proliferation TRPM2 inhibition increased cell death after doxorubicin and tamoxifen	TRPM2 expression in the nucleus was increased in cancer cells TRPM2 inhibition increased DNA damage	76,77
Gastric Cancer	Gastric cancer cell lines	TRPM2 inhibition reduced cell proliferation TRPM2 down-regulation increased cell death after doxorubicin and paclitaxel	TRPM2 inhibition decreased mitochondrial function, autophagy, bioenergetics, and JNK signaling TRPM2 inhibition increased ROS and apoptosis.	62
Lung Cancer	NSCLC patient samples Human lung cancer cell lines	Novel long non-coding RNA (TRPM2-AS) widely expressed High expression of TRPM2-AS correlated with larger tumor size, advanced TNM stage, and poor patient survival	Long non-coding RNA TRPM2-AS was associated with increased proliferation and reduced apoptosis Down regulation of TRPM2-AS reduced cell proliferation and increased apoptosis	85
	Human alveolar epithelial adenocarcinoma cells	TRPM2 inhibition reduced cell survival after irradiation	TRPM2 inhibition suppressed the DNA damage response	90
Neuroblastoma	Neuroblastoma patient samples Human neuroblastoma cell lines Xenografts	TRPM2 inhibition reduced cell viability, tumor growth in xenografts TRPM2 inhibition increased chemotherapy sensitivity	TRPM2 inhibition reduced mitochondrial function, autophagy, antioxidant response, bioenergetics, HIF-1/2a, CREB, MCU level and activity TRPM2 inhibition increased ROS levels	8,12,15,16, 61,69
Pancreatic Cancer	Patient samples Pancreatic cancer cell lines	High TRPM2 expression correlated with shorter patient survival	Higher TRPM2 expression promoted increased cell proliferation, migration, and invasion	66,89
Prostate Cancer	Pati ent Tumor Tissue Human prostate cell lines	TRPM2 inhibition reduced cancer cell proliferation	Significant TRPM2 localization in nucleus in cancer cells	67
		Long non-coding antisense TRPM2 transcripts (TRPM2-AS) are overexpressed and linked to poor patient outcome	When TRPM2-AS was reduced, a large increase in TRPM2 expression was detected, associated with increased cell apoptosis	86,87
Squamous Cell Carcinoma	Human tongue carcinoma samples Tongue carcinoma cell lines	TRPM2 inhibition reduced tumor viability	TRPM2 inhibition increased apoptosis, reduced tongue cancer cell survival, and inhibited cancer cell migration Significant TRPM2 localization to the nucleus was found in cancer cells	64,65
T-Cell Leukemia	Human leukemia cell lines	TRPM2 had a pro-survival effect and inhibition increased irradiation-induced cell death	TRPM2 inhibition decreased phosphorylation of CAMKII, reduced cells in G2/M cell cycle arrest, blocked inactivation of cdc2, and increased cell death	84