Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene

Aoki, Koji; Taketo, Makoto Mark

doi:10.1242/jcs.03485

Cited by 420 publications

(359 citation statements)

References 100 publications

(77 reference statements)

Supporting

Mentioning

351

Contrasting

Unclassified

Order By: Relevance

“…(iii) Finally, a Kaplan–Meier survival analysis further narrowed down this list to 177 candidate tumor suppressors whose downregulation is negatively correlated with patient survival (and thus, likely to enhance tumor progression; see Materials and Methods, Fig 1A and Table EV3). Reassuringly, the resulting list includes several known colon tumor suppressors such as APC (Fearnhead et al , 2001; Aoki & Taketo, 2007), TCF7L2 (Hazra et al , 2008; Slattery et al , 2008), MCC (Kinzler et al , 1991), PTEN (Nassif et al , 2004; Song et al , 2012), and SMAD4 (Miyaki et al , 1999; Alazzouzi et al , 2005). It also includes 34 metabolic genes that are present in the human metabolic model (Table EV4), and which we further studied in the next modeling step.…”

Section: Resultsmentioning

confidence: 99%

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

Auslander

Cunningham

Toosi

et al. 2017

Molecular Systems Biology

View full text Add to dashboard Cite

Metabolic alterations play an important role in cancer and yet, few metabolic cancer driver genes are known. Here we perform a combined genomic and metabolic modeling analysis searching for metabolic drivers of colorectal cancer. Our analysis predicts FUT9, which catalyzes the biosynthesis of Ley glycolipids, as a driver of advanced‐stage colon cancer. Experimental testing reveals FUT9's complex dual role; while its knockdown enhances proliferation and migration in monolayers, it suppresses colon cancer cells expansion in tumorspheres and inhibits tumor development in a mouse xenograft models. These results suggest that FUT9's inhibition may attenuate tumor‐initiating cells (TICs) that are known to dominate tumorspheres and early tumor growth, but promote bulk tumor cells. In agreement, we find that FUT9 silencing decreases the expression of the colorectal cancer TIC marker CD44 and the level of the OCT4 transcription factor, which is known to support cancer stemness. Beyond its current application, this work presents a novel genomic and metabolic modeling computational approach that can facilitate the systematic discovery of metabolic driver genes in other types of cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

Auslander

Cunningham

Toosi

et al. 2017

Molecular Systems Biology

View full text Add to dashboard Cite

show abstract

“…APC encodes for the approximately 300 kD APC protein involved in cell proliferation, migration, adhesion and cytoskeletal stabilization [2]. APC functions in the canonical (b-catenin-dependent) Wnt signaling pathway and regulates the cytoplasmic pool of b-catenin protein [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…The N-terminal phosphorylation leads b-catenin to ubiquitination and proteasomal degradation [16]. When activating Wnt ligands are present, they bind to the frizzled and LRP5/6 (low density lipoprotein-related proteins 5 and 6) cognate receptor complex located at the cell surface resulting in inhibition of b-catenin phosphorylation and/or ubiquitination by the destruction complex [15,17]. Consequently, destruction of the free pool of b-catenin is abrogated, active b-catenin accumulates in the cytoplasm and translocates in the nucleus, where it complexes with the DNA binding proteins of the TCF (T cell factor family)/Lef (lymphoid enhancer family) family, functioning as a transcriptional co-activator [18,19].…”

Section: Discussionmentioning

confidence: 99%

Orthokeratinized Odontogenic Cyst with an Associated Keratocystic Odontogenic Tumor Component and Ghost Cell Keratinization and Calcifications in a Patient with Gardner Syndrome

Argyris

Koutlas

2016

Head and Neck Pathol

View full text Add to dashboard Cite

Gardner syndrome (GS) is caused by mutations in the APC and besides adenomatous colorectal polyps includes such manifestations as osteomas, epidermoid cysts (ECs) and occasionally multiple pilomatricomas. More than 50 % of ECs in patients with GS exhibit pilomatricoma-like ghost cell keratinization. The latter may be explained by the fact that the development of both GS and pilomatricoma is driven by activation of the Wnt/b-catenin signaling pathway. A 62-year-old, Caucasian male with history of GS presented with a unilocular, mixed radiopaque/radiolucent mandibular lesion causing divergence and external root resorption of involved teeth. Histopathologically, the lesion was composed of two cystic components, an orthokeratinized odontogenic cyst (OOC) and a smaller one with characteristics of keratocystic odontogenic tumor (KCOT) featuring, focally, ghost cells and an epithelial morule-like structure. Dystrophic calcifications essentially similar to those seen in pilomatricomas were observed in the fibrous connective tissue wall. The KCOT and OOC epithelia revealed strong and diffuse cytokeratin (AE1/AE3) and b-catenin immunoreactivity. CD10 positive immunostaining was seen in the keratin and superficial spinous cell layers in both OOC and KCOT. The intraepithelial and mural ghost cells showed a cytokeratin (?), b-catenin and CD10 (-) immunophenotype. The diagnosis of OOC with ghost cell calcifications in association with KCOT was rendered. The patient was lost to follow-up. Although a coincidental co-existence cannot be excluded, ghost cell calcifications mimicking pilomatricoma-like changes in an unusual odontogenic cyst combining OOC and KCOT features as seen in this patient with GS may be explained by the common molecular mechanisms underlying the pathogenesis of cutaneous pilomatricomas and GS.

show abstract

“…Cilia serve as a switch between classic Wnt signal pathway and Wnt pathway. The cliliary defect can result in the enhancement of the classic Wnt signaling pathway (Aoki and Taketo, 2007). Although in the APC-mutated cells, APC is not able to downregulate b-catenin.…”

Section: Study On Apc Mutation and Cilia-related Diseasesmentioning

confidence: 99%

Cilia, adenomatous polyposis coli and associated diseases

Song

et al. 2011

Oncogene

View full text Add to dashboard Cite

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.

show abstract

Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene

Cited by 420 publications

References 100 publications

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

Orthokeratinized Odontogenic Cyst with an Associated Keratocystic Odontogenic Tumor Component and Ghost Cell Keratinization and Calcifications in a Patient with Gardner Syndrome

Cilia, adenomatous polyposis coli and associated diseases

Contact Info

Product

Resources

About