Table 2.
Profile expression of ion channels in pancreatic ductal adenocarcinoma (PDAC) cell lines and tissue and how they are involved in driving PDAC formation and how channel expression correlate with clinical factors.
| Channel | Profile expression Up/Downregulated (method used for expression profiling) | Cell line/Solid tumor | Driving PDAC formation in form of | Downstream regulation and signaling | Channel expression correlates with clinical factors | Ref. |
|---|---|---|---|---|---|---|
| Potassium | ||||||
| KCa3.1 | Upregulated (mRNA, IHC, Microarray, electrophysiological, transcriptome data, TCGA analysis) |
BxPC-3 Capan-1 MiaPaCa-2 PANC-1 Solid tumors |
Proliferation Cell cycle progression Migration Invasion |
Ras Oxidative Phosphorylation |
High expression: Low overall survival Advanced tumor stage |
(Bonito et al., 2016) (Jager et al., 2004) (Hayashi et al., 2012) (Jiang et al., 2017) (Shen et al., 2017) (Kovalenko et al., 2016) (Zaccagnino et al., 2016) |
| KCa4.1 | mRNA | Capan-1 PANC-1 |
(Hayashi et al., 2012) | |||
| KCa4.2 | mRNA | CFPAC PANC-1 |
(Hayashi et al., 2012) | |||
| Kv1.3 | Downregulated in tumors (mRNA, IHC) Upregulated in cell lines (mRNA, protein) |
AsPC-1 BxPC-3 Capan-1 Colo357 MiaPaCa-2 Panc-89 Panc-TUI Solid tumors |
Apoptosis Hypermethylation |
Low expression: Hypermethylation correlates with survival (not significant) | (Brevet et al., 2009) (Zaccagnino et al., 2017) (Bielanska et al., 2009) |
|
| Kv1.5 | Upregulated (IHC) |
Solid tumors | (Bielanska et al., 2009) | |||
| Kv7.1 | Downregulated (Microarray, Nanostring electrophysiological) |
A818–6 HPAF Solid tumors |
(Tawfik et al., 2020) (Fong et al., 2003) (Zaccagnino et al., 2016) |
|||
| minK | Downregulated (Microarray) |
Solid tumors | (Zaccagnino et al., 2016) | |||
| Kv10.1 | Unknown | Solid tumors | Tumor growth | Blocking shows antitumor activity | (Gomez-Varela et al., 2007) (Pardo and Stuhmer, 2014) |
|
| Kv11.1 | Upregulated (mRNA, protein, IHC, Sequencing analysis) |
BxPC-3 CFPAC-1 MiaPaCa-2 PANC-1 SW1990 T3M4 Solid tumors |
Proliferation Cell cycle progression Migration Invasion Metastasis |
miR96 EGFR-pathway ERK1/2 F-actin assembly |
High expression: Low overall survival High Ki67 expression Advanced tumor grade |
(Manoli et al., 2019) (Lastraioli et al., 2015b) (Zhou et al., 2012) (Feng et al., 2014) (Sette et al., 2013) |
| TREK-1 | Upregulated (protein, electrophysiological) |
AsPC-1 BxPC-3 Capan-1 |
Proliferation Migration |
pH/Vm activated | (Sauter et al., 2016) | |
| TASK-1 | Downregulated (Microarray database analysis) |
Solid tumors | (Williams et al., 2013) | |||
| TASK-2 | (mRNA, protein electrophysiological) |
HPAF | (Fong et al., 2003) | |||
| TWIK-1 | Upregulated (Microarray database analysis) |
Solid tumors | (Williams et al., 2013) | |||
| TWIK-3 | Downregulated (Microarray) |
Solid tumors | Cell differentiation | (Zaccagnino et al., 2016) | ||
| Kir3.1 | Upregulated (mRNA, IHC) |
Solid tumors | (Brevet et al., 2009) | |||
| Kir4.2 | Downregulated (Microarray) |
Solid tumors | Cell differentiation | (Zaccagnino et al., 2016) | ||
| Kir5.1 | Downregulated (Microarray) |
Solid tumors | (Zaccagnino et al., 2016) | |||
| Sodium | ||||||
| VGSC SCN9A SCNA3 |
Downregulated (Microarray) |
MiaPaCa-2 CAV Solid tumors |
Proliferation | Inhibition of growth with phenytoin | (Sato et al., 1994; Koltai, 2015) (Zaccagnino et al., 2016) |
|
| ASIC1 | Upregulated (mRNA, protein, IHC) |
AsPC-1 BxPC-3 PANC-1 SW1990 Solid tumors |
EMT Metastasis |
RhoA | (Zhu et al., 2017) | |
| ASIC3 | Upregulated (mRNA, protein, IHC) |
AsPC-1 BxPC-3 PANC-1 SW1990 Solid tumors |
EMT Metastasis |
RhoA | (Zhu et al., 2017) | |
| Calcium | ||||||
| ORAI1 | Different expression in different cell lines (mRNA, protein) Downregulated (Microarray) |
AsPC-1 BxPC-3 Capan-1 MiaPaCa-2 PANC-1 Solid tumors |
Apoptosis Proliferation |
Calcium-regulated Akt/mTOR/NFAT signaling | (Kondratska et al., 2014) (Khan et al., 2020) (Zaccagnino et al., 2016) |
|
| STIM1 | Different expression in different cell lines Upregulated in chemo-resistant cells (mRNA, protein,TCGA analysis, IHC) |
AsPC‐1 BxPC‐3 Capan-1 CFAPC‐1 MiaPaCa2 Panc‐1 Solid tumors |
Apoptosis Proliferation Invasion EMT Gemcitabine resistance |
Regulated by HIF1-alpha | High expression: Low disease-free survival Advanced tumor grade |
(Kondratska et al., 2014) (Zhou et al., 2020) (Wang et al., 2019) |
| TRPM2 | Upregulated (mRNA, TCGA analysis) |
PANC-1 Solid tumors |
Proliferation Migration Invasion |
High expression: Low overall survival |
(Lin et al., 2018) Reviewed in: (Stoklosa et al., 2020) |
|
| TRPM7 | Upregulated (mRNA, protein, IHC, electrophysiological) |
BxPC‐3 Capan-1 HPAF-II MiaPaCa2 PL45 Panc‐1 Panc 02.03 Solid tumors |
Proliferation Cell cycle progression Migration Invasion |
Mg2+-sensitive Socs3a-pathway Hsp90α/uPA/ MMP-2 proteolytic axis |
High expression: Low overall survival Advanced tumor grade Advanced tumor stage Large tumor size Metastasis Molecular phenotype Treatment response |
(Yee et al., 2011; Yee et al., 2012a; Yee et al., 2015) (Rybarczyk et al., 2012; Rybarczyk et al., 2017) |
| TRPM8 | Upregulated (mRNA, protein, IHC, electrophysiological) |
BxPC‐3 Capan-1 HPAF-II MiaPaCa2 Panc‐1 Panc 02.03 PL45 Solid tumors |
Proliferation Cell cycle progression Apoptosis Invasion Migration |
Glycosylation states | High expression: Low overall survival Low disease-free survival Poor prognosis Metastasis Molecular phenotype Treatment response |
(Yee et al., 2010) (Yee et al., 2012a) (Liu et al., 2018) (Yee et al., 2014) (Du et al., 2018) (Cucu et al., 2014) (Ulareanu et al., 2017) |
| TRPC1 | (mRNA, protein) | BxPC-1 CAPAN-1 CFPAC PANC-1 |
Motility | TGF-β-induced Ca/PKCα signaling | (Kim et al., 2013) (Dong et al., 2010) |
|
| TRPC4 | (mRNA, protein) | BxPC-1 | (Dong et al., 2010) | |||
| TRPC6 | (mRNA, protein) | BxPC-1 | (Dong et al., 2010) | |||
| TRPV1 | Upregulated (mRNA, protein, IHC) |
Capan-1 MiaPaCa-2 PANC-1 Solid tumors |
Proliferation Apoptosis |
EGFR/MAPK | (Huang et al., 2020) (Hartel et al., 2006) Reviewed in: (Liddle, 2007) |
|
| TRPV6 | Upregulated (mRNA, protein, IHC) Downregulated (Microarray, Nanostring) |
A818-6 AsPC-1 BxPC-3 CAPAN-1 CFPAC PANC-1 SW1990 Solid tumors |
Cell cycle Apoptosis Metastasis |
Numb protein | High expression: Low overall survival Advanced tumor stage Large tumor size Vascular infiltration |
(Kim et al., 2013; Song et al., 2018) (Tawfik et al., 2020) (Zaccagnino et al., 2016) |
| IP3R | Immunoblotting (IF) | PANC-1 | Migration | Colocalization with STIM1/ER–PM junctions | (Okeke et al., 2016) | |
| CACNA1 | Upregulated (Microarray) | Solid tumors | (Zaccagnino et al., 2016) | |||
| CACNA1G | Downregulated | Solid tumors | (Zaccagnino et al., 2016) | |||
| Chloride | ||||||
| CLCA1 | Upregulated (IHC, Proteomics) |
Solid tumors | Unclear | Low expression correlates with poor prognosis Low overall survival |
(Hu et al., 2018a) (Hu et al., 2018b; Hu et al., 2019) |
|
| CLCNKB | Downregulated (Microarray) |
Solid tumors | (Zaccagnino et al., 2016) | |||
| CLCN1 | Downregulated (Microarray) |
Solid tumors | (Zaccagnino et al., 2016) | |||
| CLIC1 | Upregulated (IHC) |
MiaPaCa-2 PANC-1 Solid tumors |
Proliferation Invasion |
High expression: Low overall survival Advanced tumor grade Advanced tumor stage Large tumor size |
(Jia et al., 2016) (Lu et al., 2015) |
|
| CLIC2 | mRNA, protein, electrophysiological | HPAF | (Fong et al., 2003) | |||
| CLIC3 | Upregulated (mRNA, protein, electrophysiological, immunohistochemistry) |
HPAF Solid tumors |
Promote integrin recycling | High expression: Low overall survival |
(Dozynkiewicz et al., 2012) (Fong et al., 2003) |
|
| CLIC4 | Upregulated (IHC) |
Solid tumors | Invasion | (Zou et al., 2016) | ||
| CLIC5 | (mRNA, protein electrophysiological) Downregulated (Microarray) |
HPAF Solid tumors |
Cell differentiation | (Fong et al., 2003) (Zaccagnino et al., 2016) |
||
| TMEM16A | Upregulated (mRNA, electrophysilogical, TCGA analysis) |
AsPC-1 BxPC-3 Capan-1 MiaPaCa-2 PANC-1 Solid tumors |
Migration | TMEM16A-dependent store-operated calcium entry (SOCE). EGFR-signaling pathways |
High expression: Low overall survival |
(Sauter et al., 2015) (Wang and Novak, 2013) (Crottes et al., 2019) |
| TMEM16E | Upregulated (mRNA, protein, IHC) |
BxPC-3 HPAC PANC-1 Solid tumors |
Proliferation Migration |
(Song et al., 2019) | ||
| TMEM16J | Upregulated (mRNA, protein, IHC) |
AsPC-1 BxPC-3 Capan-2 PANC-1 Solid tumors |
Proliferation | ERK1/2 EGFR |
High expression: Low overall survival |
(Jun et al., 2017) |
| CFTR | Downregulated (mRNA, Microarray, Sequencing analysis) Immunoblotting (IF) |
AsPC-1 BxPC-3 Capan-1 Capan-2 Colo357 CFPAC1 HPAC HPAF HS766T MiaPaCa-2 PANC-1 QGP1 S2CP9 Suit2 SW1990 T3M4 Solid tumors Organoids |
EMT | Regulate expression of MUC4 | CFTR mutation leads to a higher risk of getting pancreatic cancer | (Chambers and Harris, 1993) (Singh et al., 2007) (McWilliams et al., 2010; Cazacu et al., 2018) (Hennig et al., 2019) (Zaccagnino et al., 2016) |
| Aquaporins | ||||||
| AQP1 | Upregulated (mRNA, protein, IHC) |
Solid tumors | High expression: Low overall survival Advanced tumor stage Large tumor size Lymph node metastasis Tumor differentiation Invasion |
(Burghardt et al., 2003) (Zou et al., 2019) |
||
| AQP3 | Upregulated (mRNA, Microarray, protein, IHC) |
BxPC-3 Capan-2 HPAC HPAFII Solid tumors |
Proliferation Apoptosis EMT |
mTOR/S6 signaling Simultaneous overexpression of EGFR, Ki-67, and CK7, down-regulation of E-cadherin and vimentin |
High expression: Low overall survival Advanced tumor stage Large tumor size Lymph node metastasis Tumor differentiation Invasion |
(Burghardt et al., 2003) (Huang et al., 2017) (Zou et al., 2019) (Direito et al., 2017) (Zaccagnino et al., 2016) |
| AQP4 | (mRNA) | Capan-1 Capan-2 Solid tumors |
(Burghardt et al., 2003) | |||
| AQP5 | Upregulated (mRNA, IHC) |
Capan-1 Capan-2 HPAF Solid tumors |
Proliferation Differentiation EMT |
Simultaneous overexpression of EGFR, Ki-67, and CK7. Downregulation of E-cadhering and vimentin. |
High expression: Low overall survival Tumor differentiation |
(Burghardt et al., 2003) (Direito et al., 2017) |
| AQP8 | mRNA Downregulated (Microarray) |
Solid tumors | (Burghardt et al., 2003) (Zaccagnino et al., 2016) |
|||
| Ionotropic receptors | ||||||
| P2X4 | mRNA | AsPC-1 BxPC-3 Capan-1 CFPAC-1 MiaPaCa-2 PANC-1 |
(Kunzli et al., 2007) (Hansen et al., 2008) (Giannuzzo et al., 2015) |
|||
| P2X6 | mRNA | AsPC-1 BxPC-3 Capan-1 CFPAC-1 MiaPaCa-2 PANC-1 |
(Kunzli et al., 2007) (Hansen et al., 2008) (Giannuzzo et al., 2015) |
|||
| P2X7 | Upregulated (mRNA, protein, IHC) |
AsPC-1 BxPC-3 Capan-1 CFPAC-1 MiaPaCa-2 PANC-1 Solid tumors |
Proliferation Apoptosis Invasion Migration |
PKC, PLD ERK1/2, and JNK Decreased nitric oxide synthase |
(Giannuzzo et al., 2015) (Kunzli et al., 2007) (Hansen et al., 2008) (Choi et al., 2018) |
|
| NMDAR | (IHC, Microarray) | BxPC-3 HPAFII SUIT2 Solid tumors |
Proliferation Survival |
(Li and Hanahan, 2013) (North et al., 2017) |