TY - JOUR
T1 - Pannexin-1 expression in tumor cells correlates with colon cancer progression and survival
AU - Fierro-Arenas, Aaron
AU - Landskron, Glauben
AU - Camhi-Vainroj, Ilan
AU - Basterrechea, Benjamín
AU - Parada-Venegas, Daniela
AU - Lobos-González, Lorena
AU - Dubois-Camacho, Karen
AU - Araneda, Catalina
AU - Romero, Camila
AU - Domínguez, Antonia
AU - Vásquez, Gonzalo
AU - López-K, Francisco
AU - Alvarez, Karin
AU - González, Carlos M.
AU - Hager Ribeiro, Carolina
AU - Balboa, Elisa
AU - Eugenin, Eliseo
AU - Hermoso, Marcela A.
AU - De la Fuente López, Marjorie
N1 - Publisher Copyright:
© 2024
PY - 2024/8/15
Y1 - 2024/8/15
N2 - Aims: Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study. Main methods: PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid. Key findings: PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stage-dependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth. Significance: PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.
AB - Aims: Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study. Main methods: PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid. Key findings: PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stage-dependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth. Significance: PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.
KW - Biomarker
KW - Cancer progression
KW - Colon cancer
KW - PANX1
KW - Probenecid
KW - Therapeutic targeting
UR - https://www.scopus.com/pages/publications/85196542544
U2 - 10.1016/j.lfs.2024.122851
DO - 10.1016/j.lfs.2024.122851
M3 - Artículo
C2 - 38897345
AN - SCOPUS:85196542544
SN - 0024-3205
VL - 351
JO - Life Sciences
JF - Life Sciences
M1 - 122851
ER -