Hippo pathway in cancer cells induces NCAM1⁺αSMA⁺ fibroblasts to modulate tumor microenvironment.

ABSTRACT: Cancer cells adeptly manipulate the tumor microenvironment (TME) to evade host antitumor immunity. However, the role of cancer cell-intrinsic signaling in shaping the immunosuppressive TME remains unclear. Here, we found that the Hippo pathway in cancer cells orchestrates the TME by influencing the composition of cancer-associated fibroblasts (CAFs). In a 4T1 mouse breast cancer model, Hippo pathway kinases, large tumor suppressor 1 and 2 (LATS1/2), promoted the formation of neural cell adhesion molecule 1 (NCAM1)⁺alpha-smooth muscle actin (αSMA)⁺ CAFs expressing the transforming growth factor-β, which is associated with T cell inactivation and dysfunction. Depletion of LATS1/2 in cancer cells resulted in a less immunosuppressive TME, indicated by the reduced proporti

SUBMITTER: Thinyakul C 

PROVIDER: S-EPMC11487161 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature