Herein, it was observed that canonical ER stress biomarkers,33 such as GRP78, p‐PERK(Thr980), CHOP, IRE1α, p‐IRE1α(Ser724) and p‐JNK (Thr183/Thr183/Thr221), were enhanced by RCN1 depletion, which was in turn neutralized by human osteoblast‐CM, even offset, indicating that RCN1 produced by osteoblasts facilitated proliferation and migration of NSCLC cells, in part, through suppressing ER stress, in which decreased GRP78, CHOP, IRE1α, p‐IRE1α, p‐PERK and p‐JNK were involved, consistent with other authors’ studies in liver cancer cells38 and prostate cancer cells.40 This evidence concerns the gene HSPA5 and liver cancer.