Divya Murthy, Kuldeep S Attri, Surendra K Shukla, Ravi Thakur, Nina V Chaika, Chunbo He, Dezhen Wang, Kanupriya Jha, Aneesha Dasgupta, Ryan J King, Scott E Mulder, Joshua Souchek, Teklab Gebregiworgis, Vikant Rai, Rohit Patel, Tuo Hu, Sandeep Rana, Sai Sundeep Kollala, Camila Pacheco, Paul M Grandgenett, Fang Yu, Vikas Kumar, Audrey J Lazenby, Adrian R Black, Susanna Ulhannan, Ajay Jain, Barish H Edil, David L Klinkebiel, Robert Powers, Amarnath Natarajan, Michael A Hollingsworth, Kamiya Mehla, Quan Ly, Sarika Chaudhary, Rosa F Hwang, Kathryn E Wellen, Pankaj K Singh
The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment...
March 1, 2024: Nature Cell Biology