Exploration of Targeted Anti-tumor Therapy

Table 1. Representative studies about Ca²⁺ channels/pumps/uniporters in cancer metastasis

Channels/Pumps/Uniporters		Alteration	Events/Mechanisms	Cancer type	Reference
VGCC	Cav1.2	↑	-	CRC	[143]
	Cav1.3	↑	-	Breast cancer, endometrial carcinoma	[144, 145]
	Cav2.2	↑	EMT	Breast cancer	[146]
	Cav3.1/3.2	-	-	Glioblastoma, RAF^V600E melanoma	[147, 148]
CRAC	-	-	Upregulation of MFAP5 derived from CAFs increases SOCE in cancer cells	Ovarian cancer	[149]
	Orai1	↑	Focal adhesion turnover, invadopodium formation, EMT and extracellular matrix degradation	Glioma, melanoma and breast cancer	[13, 150–153]
	Orai2	↑	Focal adhesion disassembly	GC	[154]
	Orai3	-	Neuroendocrine-to-mesenchymal transition	Gastro-enteropancreatic neuroendocrine tumor	[151]
	STIM1	↑	Focal adhesion turnover and invadopodium formation	Melanoma, gastric and breast cancer	[13, 153, 155]
	STIM2	↑	EMT	Breast cancer	[8]
	MS4A12	↑	-	Colon cancer	[156]
TRP channel	TRPC1	↑	EMT	Breast cancer	[157]
	TRPC3	↑	-	Melanoma	[158]
	TRPC4	-	-	Medulloblastoma	[159]
	TRPC5	↑	EMT	Colon cancer	[160]
	TRPC6	↑	EMT	Breast and gastric cancer	[161–163]
	TRPM2	-	EMT	Gastric cancer	[164]
	TRPM3	↑	EMT	Renal cell carcinoma	[165]
	TRMP4	↑	EMT	Prostate cancer	[166, 167]
	TRPM5	-	MMP9	Melanoma	[168]
	TRPM7	↑	EMT	Nasopharyngeal carcinoma, ovarian and breast cancer	[169–171]
	TRPM8	↑	EMT	Colon cancer	[172]
	TRPML1	-	Lysosomal exocytosis	Hepatocellular carcinoma	[173]
	TRPP2	↑	EMT	Laryngeal squamous cell carcinoma	[174]
	TRPV1	↓	Peritoneal dissemination	GC	[175]
	TRPV2	↑	-	Prostate and esophageal cancer	[176]
	TRPV4	↑	Matrix stiffness and EMT	Endometrial and breast cancer	[177, 178]
	TRPV4	↓	Tumor vessel integrity	Prostate cancer	[179]
	TRPV5	↓	-	Renal cell carcinoma	[180]
	TRPV6	↑	-	Prostate cancer	[181]
ATP dependent pumps	PMCA4	↓	EMT	GC	[182]
	SERCA	-	Focal adhesions	Glioblastoma	[183]
	SERCA2	↑	-	Colorectal cancer	[184]
	SERCA3	↓	-	Colorectal adenoma-adenocarcinoma	[185]
	P2X7	↑	EMT and formation of filopodia	Melanoma and colon cancer	[186–188]
	P2Y	-	-	Colon cancer	[187]
	P2Y2	-	EMT	Prostate cancer	[189, 190]
	P2Y6	-	Filopodia and focal adhesions	Lung cancer	[191]
	P2Y12	-	Positive regulation of Akt in platelets	-	[192]
MCU complex	EMRE	↓	-	TNBC	[193]
	MCU	↑	ROS, MVD, tube formation and sprouting capacity	Hepatocellular carcinoma and TNBC	[194–196]
	MCUb	↓	ROS	TNBC	[196]
	MICU1	↑	ROS	TNBC	[193]
		↓	ROS	Hepatocellular carcinoma	[194]
	MICU2	↑	ROS	TNBC	[193]
	MCUR1	↑	EMT	HCC	[197]
TPCs	Tpc2	↓	EMT	Melanoma	[198]
IP₃R	IP₃R-3	↑	-	Colorectal cancer	[199]
RyR	RyR2	↓	-	Thyroid carcinoma	[200]

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↑: indicates increased; ↓: indicates decreased; -: indicates not availab; VGCC: voltage-gated Ca²⁺ channel; MFAP5: microfibrillar-associated protein 5; SOCE: store-operated Ca²⁺ entry; STIM: stromal interaction molecule; TRP: transient receptor potential; TRPC: TRP canonical; TRPM: TRP melastatin; TRPML1: Mucolipin TRP channel 1; TRPP2: TRP polycystin 2; TRPV: TRP vanilloid; PMCA: plasma membrane Ca²⁺ ATPase; GC: gastric cancer; SERCA: (Sarco)-ER Ca²⁺ ATPase; MCU: mitochondrial calcium uniporter; EMRE: essential MCU regulator; MCUb: MCU dominant negative beta subunit; MICU: mitochondrial calcium uptake; MCUR1: MCU regulator 1; TPC: two-pore channel; IP₃R: inositol 1,4,5-trisphosphate receptor; RyR: ryanodine receptor; MVD: microvessel density

Declarations

Author contributions

CCC, ZYX and WXW contributed to the conception and design of the review. CCC, ZYX, LG, ZSH and ZJH collected the related reports and drafted the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was sponsored by the National Natural Science Foundation of China (No. 81902442), Natural Science Foundation of Henan for Excellent Young Scholars (No. 202300410309), Key Scientific Research Projects of Henan for College (No. 20A320010) and Start-up Funds of Xinxiang Medical University (No. 505284). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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