The Wnt/beta-catenin Signaling Pathway Targets PPARgamma Activity in Colon Cancer Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Jan 25

PMID 15665104

Citations 73

Authors

Emmelie A Jansson

Alexandra Are

Gediminas Greicius

I-Chun Kuo

Denise Kelly

Velmurugesan Arulampalam

Sven Pettersson

Affiliations

Soon will be listed here.

Abstract

Control of colon cell fate in adenocarcinomas is disrupted, in part, due to aberrant Wnt/beta-catenin signaling. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has been implicated in the development of colon cancers. In the adenomatous polyposis coli multiple intestinal neoplasia (APCMin) mouse cancer model, PPARgamma expression in the colonic mucosa is markedly altered. In addition, PPARgamma protein levels are elevated, possibly through sequestration by activated beta-catenin in colon cancer cell lines. Induction of the Wnt/beta-catenin pathway by LiCl also elevated PPARgamma levels and induced PPARgamma-dependent reporter and endogenous target genes. Mechanistically, PPARgamma, through interactions with beta-catenin and T cell transcription factor (Tcf)-4, may be a determinant of cell fate and is likely a target of the Wnt pathway in cancer cells.

Citing Articles

Canagliflozin alleviates valproic acid-induced autism in rat pups: Role of PTEN/PDK/PPAR-γ signaling pathways.

Elgamal M, Khodeer D, Abdel-Wahab B, Ibrahim I, Alzahrani A, Moustafa Y Front Pharmacol. 2023; 14:1113966.

PMID: 36909191 PMC: 9992196. DOI: 10.3389/fphar.2023.1113966.

Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug.

Schultz C, Nevler A Biomedicines. 2022; 10(12).

PMID: 36552005 PMC: 9775650. DOI: 10.3390/biomedicines10123249.

Emerging Direct Targeting β-Catenin Agents.

Nalli M, Masci D, Urbani A, La Regina G, Silvestri R Molecules. 2022; 27(22).

PMID: 36431838 PMC: 9698307. DOI: 10.3390/molecules27227735.

Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state.

Yang X, Li G, Tian Y, Wang X, Xu J, Liu R Theranostics. 2022; 12(16):6865-6882.

PMID: 36276637 PMC: 9576623. DOI: 10.7150/thno.76619.

Alpinetin promotes hair regeneration via activating hair follicle stem cells.

Fan X, Chen J, Zhang Y, Wang S, Zhong W, Yuan H Chin Med. 2022; 17(1):63.

PMID: 35637486 PMC: 9153166. DOI: 10.1186/s13020-022-00619-2.

References

Powell S, Zilz N, Bryan T, Hamilton S, Thibodeau S, Vogelstein B . APC mutations occur early during colorectal tumorigenesis. Nature. 1992; 359(6392):235-7. DOI: 10.1038/359235a0. View

Lefebvre M, Paulweber B, Fajas L, Woods J, McCRARY C, Colombel J . Peroxisome proliferator-activated receptor gamma is induced during differentiation of colon epithelium cells. J Endocrinol. 1999; 162(3):331-40. DOI: 10.1677/joe.0.1620331. View

Barker N, Morin P, Clevers H . The Yin-Yang of TCF/beta-catenin signaling. Adv Cancer Res. 1999; 77:1-24. DOI: 10.1016/s0065-230x(08)60783-6. View

Gurnell M, Wentworth J, Agostini M, Adams M, Collingwood T, Provenzano C . A dominant-negative peroxisome proliferator-activated receptor gamma (PPARgamma) mutant is a constitutive repressor and inhibits PPARgamma-mediated adipogenesis. J Biol Chem. 2000; 275(8):5754-9. DOI: 10.1074/jbc.275.8.5754. View

Truica C, Byers S, Gelmann E . Beta-catenin affects androgen receptor transcriptional activity and ligand specificity. Cancer Res. 2000; 60(17):4709-13. View

Tontonoz P, Hu E, Spiegelman B . Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994; 79(7):1147-56. DOI: 10.1016/0092-8674(94)90006-x. View

Lehmann J, Moore L, Wilkison W, Willson T, Kliewer S . An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995; 270(22):12953-6. DOI: 10.1074/jbc.270.22.12953. View

Mangelsdorf D, Evans R . The RXR heterodimers and orphan receptors. Cell. 1995; 83(6):841-50. DOI: 10.1016/0092-8674(95)90200-7. View

Mansen A, Rafter J, Branting C, Gustafsson J . Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa. Biochem Biophys Res Commun. 1996; 222(3):844-51. DOI: 10.1006/bbrc.1996.0832. View

10.

Stambolic V, Ruel L, Woodgett J . Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol. 1996; 6(12):1664-8. DOI: 10.1016/s0960-9822(02)70790-2. View

11.

Korinek V, Barker N, Morin P, van Wichen D, de Weger R, Kinzler K . Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997; 275(5307):1784-7. DOI: 10.1126/science.275.5307.1784. View

12.

Morin P, Sparks A, Korinek V, Barker N, Clevers H, Vogelstein B . Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997; 275(5307):1787-90. DOI: 10.1126/science.275.5307.1787. View

13.

Iwamoto M, Ahnen D, Franklin W, Maltzman T . Expression of beta-catenin and full-length APC protein in normal and neoplastic colonic tissues. Carcinogenesis. 2000; 21(11):1935-40. DOI: 10.1093/carcin/21.11.1935. View

14.

Tanaka T, Kohno H, Yoshitani S, Takashima S, Okumura A, Murakami A . Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats. Cancer Res. 2001; 61(6):2424-8. View

15.

Debril M, Renaud J, Fajas L, Auwerx J . The pleiotropic functions of peroxisome proliferator-activated receptor gamma. J Mol Med (Berl). 2001; 79(1):30-47. DOI: 10.1007/s001090000145. View

16.

Palmer H, Gonzalez-Sancho J, Espada J, Berciano M, Puig I, Baulida J . Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol. 2001; 154(2):369-87. PMC: 2150773. DOI: 10.1083/jcb.200102028. View

17.

Gupta R, Brockman J, Sarraf P, Willson T, DuBois R . Target genes of peroxisome proliferator-activated receptor gamma in colorectal cancer cells. J Biol Chem. 2001; 276(32):29681-7. DOI: 10.1074/jbc.M103779200. View

18.

Hao X, Pretlow T, Rao J, Pretlow T . Beta-catenin expression is altered in human colonic aberrant crypt foci. Cancer Res. 2001; 61(22):8085-8. View

19.

Pawlowski J, Ertel J, Allen M, Xu M, Butler C, Wilson E . Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells. J Biol Chem. 2002; 277(23):20702-10. DOI: 10.1074/jbc.M200545200. View

20.

Koutnikova H, Auwerx J . PPARgamma, an X-ceptor for Xs. Ann N Y Acad Sci. 2002; 967:28-33. DOI: 10.1111/j.1749-6632.2002.tb04260.x. View