It was shown that TME lactate downregulates CAF expression of p62 (also known as sequestosome 1 or SQSTM1), a suppressor of CAF activation and tumor progression, by decreasing the NAD+/NADH ratio and subsequent inhibition of poly(ADP-ribose)-polymerase 1 (PARP-1) activity that is required for activation of c-FOS, c-JUN and AP-1, the transcriptional complex for p62 gene expression [79]. Here, FOS is linked to neoplasm.