Given that arginine restriction suppresses SREBP1 in PDAC, we asked if arginine restriction in the TME would impair the ability of mPDAC cells to cope with lipid starvation. Addition of arginine to TIFM increased the induction of SREBP1 and SREBP1 target gene expression upon lipid starvation in mPDAC cells. We next asked if impaired SREBP1 signaling and de novo lipogenesis would prevent arginine-restricted PDAC cells from maintaining lipid homeostasis under lipid starvation. In contrast, lipid starvation did not lead to separate clustering in PDAC cells cultured with supplemental arginine (Figure 3I). However, we found that we were unable to express mature SREBP1 in TIFM-cultured mPDAC cells, despite successful overexpression in RPMI-cultured mPDAC cells (Figure 3—figure supplement 4A).