We propose that while the loss of Cx43 expression contributes to breast cancer initiation by perturbing apical polarity and normal morphology (Bazzoun/Adissu et al., submitted), it activates invasion pathways that become effective under permissive mechano-transducing cues from the matrix, suggesting a long-lasting impact for Cx43 loss on breast cancer development. The gene discussed is GJA1; the disease is breast cancer.