Aryl hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis

ABSTRACT: Aryl hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl hydrocarbon receptor-mediated signaling, is overexpressed in highly metastatic human KM12SM CRC cells, with high metastatic capacity to liver, and other highly metastatic CRC cells. Meta-analysis and immunohistochemistry were used to assess the relevance of this protein in CRC. Cellular functions and signaling mechanisms mediated by AIP were assessed by gain-of-function experiments and in vitro and in vivo experiments. A significant association of high AIP expression with poor CRC patients’ survival was observed. Gain-of-function and quantitative proteomics experiments demonstrated that AIP increased tumorigenic and metastatic properties of isogenic KM12C (poorly-metastatic) and KM12SM CRC cells. AIP overexpression dysregulated epithelial-to-mesenchymal (EMT) markers and induced several transcription factors and Cadherin-17 activation. The former induced the signaling activation of AKT, SRC, and JNK kinases to increase adhesion, migration and invasion of CRC cells. In vivo, AIP expressing KM12 cells induced tumor growth and liver metastasis. Furthermore, KM12C (poorly-metastatic) cells ectopically expressing AIP became metastatic to liver. Our data reveal new roles for AIP in regulating proteins associated with cancer and metastasis to induce tumorigenic and metastatic properties in colon cancer cells driving liver metastasis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Ana Montero Calle  

LAB HEAD: Rodrigo Barderas

PROVIDER: PXD031119 | Pride | 2023-05-10

REPOSITORIES: Pride