SMAD4 and neoplasm: Furthermore, SMAD4 indirectly shapes a tumor-promoting microenvironment through the transcriptional regulation of inflammatory factors and the impact on tumor cell metabolism.56 For example, the absence of SMAD4 may lead to an abnormal increase in glycolysis and fatty acid metabolism in tumor cells.40,57,58 These metabolic changes not only support tumor cell proliferation but may also affect the function of immune cells, further modulating core immune responses.59