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Article

Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway

1
Department of Sciences, University of Basilicata, viale Ateneo Lucano 10, 85100 Potenza, Italy
2
Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028 Rionero in Vulture, Italy
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(6), 1410; https://doi.org/10.3390/cells9061410
Received: 19 March 2020 / Revised: 29 May 2020 / Accepted: 1 June 2020 / Published: 5 June 2020
(This article belongs to the Special Issue ABC Transporters: From Basic Functions to Diseases)
ABCC6, belonging to sub-family C of ATP-binding cassette transporter, is an ATP-dependent transporter mainly present in the basolateral plasma membrane of hepatic and kidney cells. Although the substrates transported are still uncertain, ABCC6 has been shown to promote ATP release. The extracellular ATP and its derivatives di- and mono-nucleotides and adenosine by acting on specific receptors activate the so-called purinergic pathway, which in turn controls relevant cellular functions such as cell immunity, inflammation, and cancer. Here, we analyzed the effect of Abcc6 knockdown and probenecid-induced ABCC6 inhibition on cell cycle, cytoskeleton, and motility of HepG2 cells. Gene and protein expression were evaluated by quantitative Reverse Transcription PCR (RT-qPCR) and western blot, respectively. Cellular cycle analysis was evaluated by flow cytometry. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by in vitro wound-healing migration assay. Cell migration is reduced both in Abcc6 knockdown HepG2 cells and in probenecid treated HepG2 cells by interfering with the extracellular reserve of ATP. Therefore, ABCC6 could contribute to cytoskeleton rearrangements and cell motility through purinergic signaling. Altogether, our findings shed light on a new role of the ABCC6 transporter in HepG2 cells and suggest that its inhibitor/s could be considered potential anti-metastatic drugs. View Full-Text
Keywords: ABCC6; HepG2; probenecid; purinergic pathway; ATP; cytoskeleton; cell motility ABCC6; HepG2; probenecid; purinergic pathway; ATP; cytoskeleton; cell motility
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MDPI and ACS Style

Ostuni, A.; Carmosino, M.; Miglionico, R.; Abruzzese, V.; Martinelli, F.; Russo, D.; Laurenzana, I.; Petillo, A.; Bisaccia, F. Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway. Cells 2020, 9, 1410. https://doi.org/10.3390/cells9061410

AMA Style

Ostuni A, Carmosino M, Miglionico R, Abruzzese V, Martinelli F, Russo D, Laurenzana I, Petillo A, Bisaccia F. Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway. Cells. 2020; 9(6):1410. https://doi.org/10.3390/cells9061410

Chicago/Turabian Style

Ostuni, Angela, Monica Carmosino, Rocchina Miglionico, Vittorio Abruzzese, Fabio Martinelli, Daniela Russo, Ilaria Laurenzana, Agata Petillo, and Faustino Bisaccia. 2020. "Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway" Cells 9, no. 6: 1410. https://doi.org/10.3390/cells9061410

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