Abstract A005: Adherent-to-suspension transition by hematopoietic factors promotes metastatic dissemination

Abstract

Abstract How primary tumor cells reprogram their anchorage dependency to disseminate into the bloodstream remain elusive. Here, we discover a biological phenomenon referred to as “Adherent-to-Suspension Transition” (AST) that reprograms adherent cells into suspension cells by introducing four hematopoietic transcriptional regulators, which we designated AST factors. Induction of AST factors in adherent cells suppress Hippo transducers YAP-TEAD and upregulate globin genes that evoke spontaneous cell-matrix dissociation and anoikis resistance in the absence of lineage differentiation. During dissemination, we uncover the aberrant induction of AST factors in circulating tumor cells (CTCs) derived from de novo metastatic breast cancer patients and mouse models in vivo. Pharmacological blockade of AST factors in breast cancer cells abrogates CTC formation and suppresses lung metastases without affecting the primary tumor growth. Collectively, we demonstrate that suspension cells can directly arise from adherent cells by the addition of defined factors that confer metastatic traits. Furthermore, our data expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer. Citation Format: Hyunbin D. Huh, Heon Yung Gee, Hyun Woo Park. Adherent-to-suspension transition by hematopoietic factors promotes metastatic dissemination [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A005.