Seeding cells onto substrates that stimulate β1 integrins increased hERG1 current density and Vrest hyperpolarization, an effect not observed with BSA or Polylysine.
Extracellular matrix proteins stimulate β1 integrins to modulate hERG1 current density, highlighting a functional interaction relevant to cancer cell models.
Ion channels are implicated in various diseases, including cancer, in which they modulate different aspects of cancer progression. In particular, potassium channels are often aberrantly expressed in cancers, a major example being provided by hERG1. The latter is generally complexed with β1 integrin in tumour cells, and such a molecular complex represents a new druggable hub. The present study focuses on the characterization of the functional consequences of the interaction between hERG1 and β1 integrins on different substrates over time. To this purpose, we studied the interplay alteration on the plasma membrane through patch clamp techniques in a cellular model consisting of human embryonic kidney (HEK) cells stably transfected with hERG1 and in a cancer cell model consisting of SH-SY5Y neuroblastoma cells, endogenously expressing the channel. Cells were seeded on different substrates known to stimulate β1 integrins, such as fibronectin (FN) for HEK-hERG1 and laminin (LMN) for SH-SY5Y. In HEK cells stably overexpressing hERG1, we observed a hERG1 current density increase accompanied by Vrest hyperpolarization after cell seeding onto FN. Notably, a similar behaviour was shown by SH-SY5Y neuroblastoma cells plated onto LMN. Interestingly, we did not observe this phenomenon when plating the cells on substrates such as Bovine Serum Albumin (BSA) or Polylysine (PL), thus suggesting a crucial involvement of ECM proteins as well as of β1 integrin activation.
Altadonna et al. (Fri,) conducted a other in Cancer (neuroblastoma cell models). Substrates stimulating β1 integrins (fibronectin, laminin) vs. Substrates not stimulating β1 integrins (Bovine Serum Albumin, Polylysine) was evaluated on hERG1 current density and Vrest hyperpolarization. Seeding cells onto substrates that stimulate β1 integrins increased hERG1 current density and Vrest hyperpolarization, an effect not observed with BSA or Polylysine.