The transcription factor ATF5 plays a vital role in the formation of several cancers, including breast, lung, ovarian, pancreatic, rectal, and liver cancer. But ATF5’s function in esophageal cancer—one of the most common forms of cancer worldwide—remains unclear. To find out, researchers monitored the activity of ATF5 in esophageal cancer tissues. Much like in other cancers, ATF5 was upregulated in esophageal cancer tissues cultured in the lab, and ATF5 overexpression promoted the proliferation, migration, and invasiveness of esophageal cancer cells. Silencing ATF5, however, inhibited these abilities. In fact, in mice, silencing ATF5 hampered tumor growth. ATF5’s role as a lever that triggers tumor growth is believed to occur through an interaction with HIF1, a protein complex also known to promote the growth and spread of tumors. These findings suggest that the known anti-cancer effects of silencing ATF5 might also be powerful against esophageal cancer. Understanding how ATF5 and HIF1 interact in humans could lead to new treatments for fighting esophageal cancer.