Substrate Rigidity Dictates Colorectal Tumorigenic Cell Stemness and Metastasis via KIAA1211 Dependent Mechanotransduction

Recurrence and metastasis rank among the most prominent clinical problems in colorectal cancer (CRC) treatment. Colorectal tumorigenic cell was identified to explore the process of CRC stemness maintenance and progression by simulating tumor mechanical properties. Here, we show that F-actin regulator KIAA1211 negatively correlates with CRC progression, stemness, and metastasis. Mechanistically, decreased KIAA1211 in soft substrates induces YAP retention in the cytoplasm, restores the repression effect on stemness markers NANOG and OCT4, thereby promotes CRC stemness and metastasis. Furthermore, KIAA1211 deficiency promotes colorectal tumor cell softening and regulates EMT states, contributing to its metastasis potential. Clinically, KIAA1211 expression is correlated with malignant degrees and metastasis in CRC patients. To sum up, our work uncovers an essential role of actin regulator KIAA1211 in anti-cancer and mechanical signal transduction of extracellular matrix in CRC.