SMAD4 Controls Cancer Cell Metabolism by Regulating Methylmalonic Aciduria Cobalamin Deficiency (cbl) B Type |
Song, Kyoung
(College of Pharmacy, Duksung Women's University)
Lee, Hun Seok (Laboratory of Molecular Pathology and Cancer Genomics, Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University) Jia, Lina (Department of Pharmacology, Shenyang Pharmaceutical University) Chelakkot, Chaithanya (Bio-MAX Institute, Seoul National University) Rajasekaran, Nirmal (Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University) Shin, Young Kee (Laboratory of Molecular Pathology and Cancer Genomics, Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University) |
1 | Rosenberg, L.E., Lilljeqvist, A., and Hsia, Y.E. (1968b). Methylmalonic aciduria: metabolic block localization and vitamin B 12 dependency. Science 162, 805-807. DOI |
2 | Itatani, Y., Kawada, K., and Sakai, Y. (2019). Transforming growth factor-beta signaling pathway in colorectal cancer and its tumor microenvironment. Int. J. Mol. Sci. 20, 5822. DOI |
3 | Allen, E.L., Ulanet, D.B., Pirman, D., Mahoney, C.E., Coco, J., Si, Y., Chen, Y., Huang, L., Ren, J., Choe, S., et al. (2016). Differential aspartate usage identifies a subset of cancer cells particularly dependent on OGDH. Cell Rep. 17, 876-890. DOI |
4 | Chan, R., Mascarenhas, L., Boles, R.G., Kerkar, N., Genyk, Y., and Venkatramani, R. (2015). Hepatoblastoma in a patient with methylmalonic aciduria. Am. J. Med. Genet. A 167A, 635-638. |
5 | Anderson, N.M., Mucka, P., Kern, J.G., and Feng, H. (2018). The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell 9, 216-237. DOI |
6 | Anzmann, A.F., Pinto, S., Busa, V., Carlson, J., McRitchie, S., Sumner, S., Pandey, A., and Vernon, H.J. (2019). Multi-omics studies in cellular models of methylmalonic acidemia and propionic acidemia reveal dysregulation of serine metabolism. Biochim. Biophys. Acta Mol. Basis Dis. 1865, 165538. DOI |
7 | Allendorph, G.P., Vale, W.W., and Choe, S. (2006). Structure of the ternary signaling complex of a TGF-beta superfamily member. Proc. Natl. Acad. Sci. U. S. A. 103, 7643-7648. DOI |
8 | Bardeesy, N., Cheng, K.H., Berger, J.H., Chu, G.C., Pahler, J., Olson, P., Hezel, A.F., Horner, J., Lauwers, G.Y., Hanahan, D., et al. (2006). Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 20, 3130-3146. DOI |
9 | Biondi, C.A., Das, D., Howell, M., Islam, A., Bikoff, E.K., Hill, C.S., and Robertson, E.J. (2007). Mice develop normally in the absence of Smad4 nucleocytoplasmic shuttling. Biochem. J. 404, 235-245. DOI |
10 | Kishton, R.J. and Rathmell, J.C. (2015). Novel therapeutic targets of tumor metabolism. Cancer J. 21, 62-69. DOI |
11 | Lee, S.U., Kim, M.O., Kang, M.J., Oh, E.S., Ro, H., Lee, R.W., Song, Y.N., Jung, S., Lee, J.W., Lee, S.Y., et al. (2021). Transforming growth factor-b inhibits MUC5AC expression by SMAD3/HDAC2 complex formation and NF-kB deacetylation at K310 in NCI-H292 cells. Mol. Cells 44, 38-49. DOI |
12 | Pavlova, N.N. and Thompson, C.B. (2016). The emerging hallmarks of cancer metabolism. Cell Metab. 23, 27-47. DOI |
13 | Phillips, D., Aponte, A.M., French, S.A., Chess, D.J., and Balaban, R.S. (2009). Succinyl-CoA synthetase is a phosphate target for the activation of mitochondrial metabolism. Biochemistry 48, 7140-7149. DOI |
14 | Rajasekaran, N., Song, K., Lee, J.H., Wei, Y., Erkin, O.C., Lee, H., and Shin, Y.K. (2021). Nuclear respiratory factor-1, a novel SMAD4 binding protein, represses TGF-beta/SMAD4 signaling by functioning as a transcriptional cofactor. Int. J. Mol. Sci. 22, 5595. DOI |
15 | Lycan, T.W., Pardee, T.S., Petty, W.J., Bonomi, M., Alistar, A., Lamar, Z.S., Isom, S., Chan, M.D., Miller, A.A., and Ruiz, J. (2016). A phase II clinical trial of CPI-613 in patients with relapsed or refractory small cell lung carcinoma. PLoS One 11, e0164244. DOI |
16 | Dang, L., White, D.W., Gross, S., Bennett, B.D., Bittinger, M.A., Driggers, E.M., Fantin, V.R., Jang, H.G., Jin, S., Keenan, M.C., et al. (2009). Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462, 739-744. DOI |
17 | Bartsch, D., Hahn, S.A., Danichevski, K.D., Ramaswamy, A., Bastian, D., Galehdari, H., Barth, P., Schmiegel, W., Simon, B., and Rothmund, M. (1999). Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors. Oncogene 18, 2367-2371. DOI |
18 | Batlle, E. and Massague, J. (2019). Transforming growth factor-beta signaling in immunity and cancer. Immunity 50, 924-940. DOI |
19 | Blackford, A., Serrano, O.K., Wolfgang, C.L., Parmigiani, G., Jones, S., Zhang, X., Parsons, D.W., Lin, J.C., Leary, R.J., Eshleman, J.R., et al. (2009). SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin. Cancer Res. 15, 4674-4679. DOI |
20 | David, C.J. and Massague, J. (2018). Contextual determinants of TGFbeta action in development, immunity and cancer. Nat. Rev. Mol. Cell Biol. 19, 419-435. DOI |
21 | Dobson, C.M., Wai, T., Leclerc, D., Kadir, H., Narang, M., Lerner-Ellis, J.P., Hudson, T.J., Rosenblatt, D.S., and Gravel, R.A. (2002). Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. Hum. Mol. Genet. 11, 3361-3369. DOI |
22 | Rush, E.C., Katre, P., and Yajnik, C.S. (2014). Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease. Eur. J. Clin. Nutr. 68, 2-7. DOI |
23 | Massague, J. and Wotton, D. (2000). Transcriptional control by the TGF-beta/Smad signaling system. EMBO J. 19, 1745-1754. DOI |
24 | Papageorgis, P., Cheng, K., Ozturk, S., Gong, Y., Lambert, A.W., Abdolmaleky, H.M., Zhou, J.R., and Thiagalingam, S. (2011). Smad4 inactivation promotes malignancy and drug resistance of colon cancer. Cancer Res. 71, 998-1008. |
25 | Rosenberg, L.E., Lilljeqvist, A.C., and Hsia, Y.E. (1968a). Methylmalonic aciduria. An inborn error leading to metabolic acidosis, long-chain ketonuria and intermittent hyperglycinemia. N. Engl. J. Med. 278, 1319-1322. DOI |
26 | Schutte, M. (1999). DPC4/SMAD4 gene alterations in human cancer, and their functional implications. Ann. Oncol. 10 Suppl 4, 56-59. DOI |
27 | Wan, R., Feng, J., and Tang, L. (2021). Consequences of mutations and abnormal expression of SMAD4 in tumors and T cells. Onco Targets Ther. 14, 2531-2540. DOI |
28 | Wilentz, R.E., Iacobuzio-Donahue, C.A., Argani, P., McCarthy, D.M., Parsons, J.L., Yeo, C.J., Kern, S.E., and Hruban, R.H. (2000). Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res. 60, 2002-2006. |
29 | Williamson, J.R. and Cooper, R.H. (1980). Regulation of the citric acid cycle in mammalian systems. FEBS Lett. 117 Suppl, K73-K85. DOI |
30 | Fehling, C., Nilsson, B., and Jagerstad, M. (1979). Effect of vitamin B12 deficiency on energy-rich phosphates, glycolytic and citric acid cycle metabolites and associated amino acids in rat cerebral cortex. J. Neurochem. 32, 1115-1117. DOI |
31 | Froese, D.S. and Gravel, R.A. (2010). Genetic disorders of vitamin B(1)(2) metabolism: eight complementation groups--eight genes. Expert Rev. Mol. Med. 12, e37. DOI |
32 | Haiman, C.A., Han, Y., Feng, Y., Xia, L., Hsu, C., Sheng, X., Pooler, L.C., Patel, Y., Kolonel, L.N., Carter, E., et al. (2013). Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population. PLoS Genet. 9, e1003419. DOI |
33 | Zachar, Z., Marecek, J., Maturo, C., Gupta, S., Stuart, S.D., Howell, K., Schauble, A., Lem, J., Piramzadian, A., Karnik, S., et al. (2011). Non-redox-active lipoate derivatives disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in-vivo. J. Mol. Med. (Berl.) 89, 1137-1148. DOI |
34 | Tsujimoto, Y. (1997). Apoptosis and necrosis: intracellular ATP level as a determinant for cell death modes. Cell Death Differ. 4, 429-434. DOI |
35 | Inigo, M., Deja, S., and Burgess, S.C. (2021). Ins and outs of the TCA cycle: the central role of anaplerosis. Annu. Rev. Nutr. 41, 19-47. DOI |
36 | Johnson, K., Kirkpatrick, H., Comer, A., Hoffmann, F.M., and Laughon, A. (1999). Interaction of Smad complexes with tripartite DNA-binding sites. J. Biol. Chem. 274, 20709-20716. DOI |
37 | Cen, H., Mao, F., Aronchik, I., Fuentes, R.J., and Firestone, G.L. (2008). DEVD-NucView488: a novel class of enzyme substrates for real-time detection of caspase-3 activity in live cells. FASEB J. 22, 2243-2252. DOI |
38 | Yan, P., Klingbiel, D., Saridaki, Z., Ceppa, P., Curto, M., McKee, T.A., Roth, A., Tejpar, S., Delorenzi, M., Bosman, F.T., et al. (2016). Reduced expression of SMAD4 is associated with poor survival in colon cancer. Clin. Cancer Res. 22, 3037-3047. DOI |
39 | Yen, K., Travins, J., Wang, F., David, M.D., Artin, E., Straley, K., Padyana, A., Gross, S., DeLaBarre, B., Tobin, E., et al. (2017). AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutation. Cancer Discov. 7, 478-493. DOI |
40 | Yuneva, M.O., Fan, T.W., Allen, T.D., Higashi, R.M., Ferraris, D.V., Tsukamoto, T., Mates, J.M., Alonso, F.J., Wang, C., Seo, Y., et al. (2012). The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 15, 157-170. DOI |
41 | Zamaraeva, M.V., Sabirov, R.Z., Maeno, E., Ando-Akatsuka, Y., Bessonova, S.V., and Okada, Y. (2005). Cells die with increased cytosolic ATP during apoptosis: a bioluminescence study with intracellular luciferase. Cell Death Differ. 12, 1390-1397. DOI |
42 | Zhang, J., Dobson, C.M., Wu, X., Lerner-Ellis, J., Rosenblatt, D.S., and Gravel, R.A. (2006). Impact of cblB mutations on the function of ATP:cob(I)alamin adenosyltransferase in disorders of vitamin B12 metabolism. Mol. Genet. Metab. 87, 315-322. DOI |
43 | McCarthy, A.J. and Chetty, R. (2018). Smad4/DPC4. J. Clin. Pathol. 71, 661-664. DOI |
44 | Depeint, F., Bruce, W.R., Shangari, N., Mehta, R., and O'Brien, P.J. (2006). Mitochondrial function and toxicity: role of B vitamins on the one-carbon transfer pathways. Chem. Biol. Interact. 163, 113-132. DOI |
45 | Pardee, T.S., Lee, K., Luddy, J., Maturo, C., Rodriguez, R., Isom, S., Miller, L.D., Stadelman, K.M., Levitan, D., Hurd, D., et al. (2014). A phase I study of the first-in-class antimitochondrial metabolism agent, CPI-613, in patients with advanced hematologic malignancies. Clin. Cancer Res. 20, 5255-5264. DOI |
46 | Sorin, M., Watkins, D., Gilfix, B.M., and Rosenblatt, D.S. (2021). Methionine dependence in tumor cells: the potential role of cobalamin and MMACHC. Mol. Genet. Metab. 132, 155-161. DOI |
47 | Zawel, L., Dai, J.L., Buckhaults, P., Zhou, S., Kinzler, K.W., Vogelstein, B., and Kern, S.E. (1998). Human Smad3 and Smad4 are sequence-specific transcription activators. Mol. Cell 1, 611-617. DOI |
48 | Gomes, A.P., Ilter, D., Low, V., Drapela, S., Schild, T., Mullarky, E., Han, J., Elia, I., Broekaert, D., Rosenzweig, A., et al. (2022). Altered propionate metabolism contributes to tumour progression and aggressiveness. Nat. Metab. 4, 435-443. DOI |
49 | Grassian, A.R., Parker, S.J., Davidson, S.M., Divakaruni, A.S., Green, C.R., Zhang, X., Slocum, K.L., Pu, M., Lin, F., Vickers, C., et al. (2014). IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism. Cancer Res. 74, 3317-3331. |
50 | Ferrari, D., Stepczynska, A., Los, M., Wesselborg, S., and Schulze-Osthoff, K. (1998). Differential regulation and ATP requirement for caspase-8 and caspase-3 activation during CD95- and anticancer drug-induced apoptosis. J. Exp. Med. 188, 979-984. DOI |
51 | Pathania, D., Millard, M., and Neamati, N. (2009). Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism. Adv. Drug Deliv. Rev. 61, 1250-1275. DOI |
52 | Lee, N. and Kim, D. (2016). Cancer metabolism: fueling more than just growth. Mol. Cells 39, 847-854. DOI |
53 | Massague, J. (1998). TGF-beta signal transduction. Annu. Rev. Biochem. 67, 753-791. DOI |
54 | Miyaki, M. and Kuroki, T. (2003). Role of Smad4 (DPC4) inactivation in human cancer. Biochem. Biophys. Res. Commun. 306, 799-804. DOI |
55 | Plessl, T., Burer, C., Lutz, S., Yue, W.W., Baumgartner, M.R., and Froese, D.S. (2017). Protein destabilization and loss of protein-protein interaction are fundamental mechanisms in cblA-type methylmalonic aciduria. Hum. Mutat. 38, 988-1001. DOI |
![]() |