On the other hand, in non-cancerous kidney tubular HK-2 cells, the decreased expression of VHL, a major tumor suppressor lost in kidney cancer, induces ER stress, as supported by GRP78, IRE1α/XBP1, eIF2α, JNK and NF-kB activation, as well as upregulation of NF-kB target genes (TNFα and Il-1β) [106]. This evidence concerns the gene HSPA5 and neoplasm.