PROJECT SUMMARY/ABSTRACT (SIGNALING AND TUMOR MICROENVIRONMENT) Members of the University of Michigan (U-M) Rogel Cancer Center (Rogel) Signaling and Tumor Microenvironment (STME) Program share interests that align with five of the nine Rogel cross-cutting research themes: Tumor Microenvironment & Metabolism; Molecular Determinants; Inflammation, Microbes & Immunity; Targets & Therapeutics; and Prevention & Early Detection. STME, formerly known as the Cancer Biology (CB), was renamed to reflect the areas of strength and focus of the membership. Members of the STME Program are engaged in understanding both tumor-intrinsic and microenvironmental effects of altered signaling networks. STME Program comprises 55 members from 28 departments and four schools at the University of Michigan. STME members have $15.3M in annual cancer-relevant grant funding (DC), 88% of which comes from peer- reviewed sources (36% NCI, 44% other NIH sources). Investigators are involved in intra- and inter-programmatic interactions and actively collaborate with Rogel Cancer Center researchers within the Basic Science, Translational and Clinical Research, and Cancer Control and Population Sciences Programs. During the period of 01/01/2017 and 12/31/2021, members authored a total of 910 cancer-relevant publications, 30.7% in journals with Impact Factors > 10. The shared research interests of program members are reflected in the program’s overall scientific aims: 1) Elucidate the role of cell fate and plasticity during tissue homeostasis and cancer progression, 2) Define the heterocellular interactions that drive tumor epithelial growth and treatment response, 3) Characterize metabolic and metabolite interactions that impact cancer and growth progression. The Aims will identify cell autonomous and microenvironmental factors that alter fundamental aspects of tumor initiation, expansion, invasion and metastasis. Our main goal is to translate the mechanistic findings to improve cancer prevention, diagnosis, and treatment.