Cilia, adenomatous polyposis coli and associated diseases

Abstract

Cilium is a conservative cell organelle, found in many types of cell surfaces. Cilia are tail-like prominence protruding out of the cell surface, capable of locomotion and acting as the cell's signal transduction sensory organs with their complex structures and ingenious function. Studies have shown that ciliary pathological changes and defects are related to the development of many diseases, including renal cysts, infertility, organ reversal, obesity and so on. The inactivation and mutation of cilia-related proteins can cause tumors, such as neoplasms, intestinal cancer, myeloma, rhabdomyosarcoma and adenocarcinoma. Adenomatous polyposis coli (APC) is a kind of multifunctional protein encoded by the APC gene that participates in many vital activities of organisms. The mutation of APC can lead to familial adenomatous polyposis, and also has a role in the development of human tumors, such as gastric cancer, esophageal cancer and breast carcinoma. Recent studies indicate that the abnormal mutation of APC may lead to some diseases caused by abnormal growth of cilia. Herein, the development of studies on cilia, APC and associated diseases are summarized in brief.

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

“…52 Its protein product negatively regulates WNT signaling and its inactivation leads to β-catenin accumulation and transcriptional activation of genes (MYC, cyclin D1) related to cell proliferation. 53,54 As reported, the chromosome locus of APC is frequently deleted in GCs, [55][56][57][58][59] and its decreased copy number significantly associated with lymph node invasion and metastasis in GC patients.…”

Cilium assembly and disassembly

“…Indeed, the function of multiple tumour suppressors — including VHL, PTEN, p53, tuberous sclerosis proteins (TSC1 and TSC2) and adenomatous polyposis coli — are linked to normal ciliary assembly and function 93–98 . Mutations in the von Hippel–Lindau tumour suppressor gene ( VHL ) predispose patients to renal cysts and clear cell renal cell carcinoma, and loss of pVHL, combined with ablation of a second tumour suppressor protein (p53 or PTEN), provokes ciliary loss, kidney cyst formation and neoplastic growth 93,94 .…”

Cilia and cilia-associated proteins in cancer

“…APC has recently been identified as a regulator of ciliary function, and Gardner’s syndrome proposed to be at least partly caused by cilia dysfunction (summarized in [53,54]). Finally, despite the high rate of VHL alteration in ccRCC, inactivation of VHL is insufficient for tumor formation (summarized in [47]) and new genes are continually being identified as mutated in ccRCC [55,56,57].…”