Estrogen receptor (ER)- and progesterone receptor (PR)-dependent expression of NINJ1, a cell-surface executioner of active cell rupture, in breast cancer, with implications in prognosis

NINJ1 (Ninjurin 1) mediates plasma membrane rupture (PMR) during lytic phase in response to inducers of different programmed cell death mechanisms such as pyroptosis, which leads to release of inflammatory molecules such as HMGB1 and LDH. However, NINJ1 has not been studied in the context of breast cancer. Here, I found that NINJ1 transcript levels are higher in breast tumors than in non-malignant breast tissue. Estrogen receptor (ER)-positive or progesterone (PR)-positive breast cancer cells have higher expression of NINJ1 than ER-negative or PR-negative breast cancer cells, respectively; and, this is independent of menopausal status. In contrast, NINJ1 expression does not differ based on HER2 status, another molecular marker used to define breast cancer subtypes. Lowest expression of NINJ1 is observed in triple negative breast cancer (TNBC). Tumor stage and race might also influence NINJ1 mRNA expression levels in breast cancer. More importantly, breast cancer patients with high NINJ1 expression have a more favorable prognosis than those with low NINJ1 expression. Higher NINJ1 levels in hormone receptor (HR)-positive (ER-positive and PR-positive) breast cancer might contribute to better survival rates observed in this patient group compared to breast cancer patients with HR-negative status. Mechanistic details of how NINJ1 influence antitumor immunity and patient outcomes in breast cancer remains to be studied.