Loss of primary cilia promotes inflammation and carcinogenesis.

Primary cilia (PC) are important signaling hubs, and we here explored their role in colonic pathology. In the colon, PC are mostly present on fibroblasts, and exposure of mice to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced acute colitis decreases PC numbers. We generated conditional knockout mice with reduced numbers of PC on colonic fibroblasts.

The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium.

The R2TP chaperone cooperates with HSP90 to integrate newly synthesized proteins into multi-subunit complexes, yet its role in tissue homeostasis is unknown. Here, we generated conditional, inducible knock-out mice for Rpap3 to inactivate this core component of R2TP in the intestinal epithelium. In adult mice, Rpap3 invalidation caused destruction of the small intestinal epithelium and death within 10 days.

Cyclin A2 maintains colon homeostasis and is a prognostic factor in colorectal cancer.

To clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC), we generated mice deficient for cyclin A2 in colonic epithelial cells (CECs). Colons of these mice displayed architectural changes in the mucosa and signs of inflammation, as well as increased proliferation of CECs associated with the appearance of low- and high-grade dysplasias. The main initial events triggering those alterations in cyclin A2-deficient CECs appeared to be abnormal mitoses and DNA damage.

SNX9 promotes metastasis by enhancing cancer cell invasion via differential regulation of RhoGTPases.

Despite current advances in cancer research, metastasis remains the leading factor in cancer-related deaths. Here, we identify sorting nexin 9 (SNX9) as a new regulator of breast cancer metastasis. We detected an increase in SNX9 expression in human breast cancer metastases compared with primary tumors and demonstrated that SNX9 expression in MDA-MB-231 breast cancer cells is necessary to maintain their ability to metastasize in a chick embryo model.