Metastatic breast cancer cells disseminate to organs with a soft microenvironment. Whether and how local tissue mechanical properties influence their response to treatment remains unclear. Here we found that a soft ECM empowers redox homeostasis. Cells cultured on a soft ECM display increased peri-mitochondrial F-actin promoted by Spire1C and Arp2/3 nucleation factors, and increased DRP1- and MIEF1/2-dependent mitochondrial fission. Changes in mitochondrial dynamics lead to increased mtROS production and activate the NRF2 antioxidant transcriptional response, including increased cystine uptake and glutathione metabolism. This retrograde response endows cells with resistance to oxidative stress and ROS-dependent chemotherapy drugs. This is relevant in a mouse model of metastatic breast cancer cells dormant in the lung soft tissue, where inhibition of DRP1 and NRF2 restored cisplatin sensitivity and prevented disseminated cancer cell awakening. We propose that targeting this mitochondrial dynamics- and redox-based mechanotransduction pathway could open avenues to prevent metastatic relapse.

A new type of breast carcinoma resembling the tall cell variant of papillary thyroid carcinoma has recently been described. To date, rare cases are on record. Here, 4 new cases of the tall cell variant of papillary thyroid carcinoma of the breast are described in women aged from 45 to 80 years old. All patients presented with palpable breast nodules and were treated with quadrantectomy. One patient presented with a long clinical history and a metastatic intramammary lymph node. The patient is alive and well 3 months after surgery. The remaining 3 patients are disease free at mean 7.5 months (range, 5 to 10 months) after surgery. These data suggest that papillary thyroid-like carcinomas of the breast show malignant potential.

This study shows that low E-cadherin expression is useful for predicting lymph node metastases in cases of OSCC. The predictive value is enhanced when low E-cadherin positivity is associated with DeltaNp63 and Delta Np73L expression.