リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「LAT1 expression influences Paneth cell number and tumor development in Apcᴹⁱⁿ/⁺ mice」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

LAT1 expression influences Paneth cell number and tumor development in Apcᴹⁱⁿ/⁺ mice

Sui, Yunlong Hoshi, Namiko Ohgaki, Ryuichi Kong, Lingling Yoshida, Ryutaro Okamoto, Norihiro Kinoshita, Masato Miyazaki, Haruka Ku, Yuna Tokunaga, Eri Ito, Yuki Watanabe, Daisuke Ooi, Makoto Shinohara, Masakazu Sasaki, Kengo Zen, Yoh Kotani, Takenori Matozaki, Takashi Tian, Zibin Kanai, Yoshikatsu Kodama, Yuzo 神戸大学

2023.05

概要

Background Amino acid transporters play an important role in supplying nutrition to cells and are associated with cell proliferation. L-type amino acid transporter 1 (LAT1) is highly expressed in many types of cancers and promotes tumor growth; however, how LAT1 affects tumor development is not fully understood. Methods To investigate the role of LAT1 in intestinal tumorigenesis, mice carrying LAT1 floxed alleles that also expressed Cre recombinase from the promoter of gene encoding Villin were crossed to an Apcᴹⁱⁿ/⁺ background (LAT1ᶠˡ/ᶠˡ; vil-cre; Apcᴹⁱⁿ/⁺), which were subject to analysis; organoids derived from those mice were also analyzed. Results This study showed that LAT1 was constitutively expressed in normal crypt base cells, and its conditional deletion in the intestinal epithelium resulted in fewer Paneth cells. LAT1 deletion reduced tumor size and number in the small intestine of Apcᴹⁱⁿ/⁺ mice. Organoids derived from LAT1-deleted Apcᴹⁱⁿ/⁺ intestinal crypts displayed fewer spherical organoids with reduced Wnt/β-catenin target gene expression, suggesting a low tumor-initiation capacity. Wnt3 expression was decreased in the absence of LAT1 in the intestinal epithelium, suggesting that loss of Paneth cells due to LAT1 deficiency reduced the risk of tumor initiation by decreasing Wnt3 production. Conclusions LAT1 affects intestinal tumor development in a cell-extrinsic manner through reduced Wnt3 expression in Paneth cells. Our findings may partly explain how nutrient availability can affect the risk of tumor development in the intestines.

この論文で使われている画像

参考文献

1. Pan SY, Morrison H. Epidemiology of cancer of the small

intestine. World J Gastrointest Oncol. 2011;3:33–42.

2. Orlich MJ, Singh PN, Sabate´ J, et al. Vegetarian dietary patterns

and the risk of colorectal cancers. JAMA Intern Med.

2015;175:767–76.

123

J Gastroenterol (2023) 58:444–457

3. Breekveldt ECH, Lansdorp-Vogelaar I, Toes-Zoutendijk E, et al.

Colorectal cancer incidence, mortality, tumour characteristics,

and treatment before and after introduction of the faecal

immunochemical testing-based screening programme in the

Netherlands: a population-based study. Lancet Gastroenterol

Hepatol. 2022;7:60–8.

4. Wyness L. The role of red meat in the diet: nutrition and health

benefits. Proc Nutr Soc. 2016;75:227–32.

5. Shanware NP, Bray K, Eng CH, et al. Glutamine deprivation

stimulates mTOR-JNK-dependent chemokine secretion. Nat

Commun. 2014;5:4900.

6. Nicklin P, Bergman P, Zhang B, et al. Bidirectional transport of

amino acids regulates mTOR and autophagy. Cell.

2009;136:521–34.

7. Sun H, Olson KC, Gao C, et al. Catabolic defect of branchedchain amino acids promotes heart failure. Circulation.

2016;133:2038–49.

8. Bi X, Henry CJ. Plasma-free amino acid profiles are predictors of

cancer and diabetes development. Nutr Diabetes. 2017;7: e249.

9. Kanai Y. Amino acid transporter LAT1 (SLC7A5) as a molecular

target for cancer diagnosis and therapeutics. Pharmacol Ther.

2022;230: 107964.

10. Yan R, Zhao X, Lei J, et al. Structure of the human LAT1-4F2hc

heteromeric amino acid transporter complex. Nature.

2019;568:127–30.

11. Cormerais Y, Giuliano S, LeFloch R, et al. Genetic disruption of

the multifunctional CD98/LAT1 complex demonstrates the key

role of essential amino acid transport in the control of mTORC1

and tumor growth. Cancer Res. 2016;76:4481–92.

12. Yanagida O, Kanai Y, Chairoungdua A, et al. Human L-type

amino acid transporter 1 (LAT1): characterization of function and

expression in tumor cell lines. Biochim Biophys Acta.

2001;1514:291–302.

13. Boado RJ, Li JY, Nagaya M, et al. Selective expression of the

large neutral amino acid transporter at the blood-brain barrier.

Proc Natl Acad Sci USA. 1999;96:12079–84.

14. Kaira K, Sunose Y, Arakawa K, et al. Prognostic significance of

L-type amino-acid transporter 1 expression in surgically resected

pancreatic cancer. Br J Cancer. 2012;107:632–8.

15. Furuya M, Horiguchi J, Nakajima H, et al. Correlation of L-type

amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis. Cancer Sci. 2012;103:382–9.

16. Takeuchi K, Ogata S, Nakanishi K, et al. LAT1 expression in

non-small-cell lung carcinomas: analyses by semiquantitative

reverse transcription-PCR (237 cases) and immunohistochemistry

(295 cases). Lung Cancer. 2010;68:58–65.

17. Sakata T, Hana K, Mikami T, et al. Positive correlation of

expression of L-type amino-acid transporter 1 with colorectal

tumor progression and prognosis: higher expression in sporadic

colorectal tumors compared with ulcerative colitis-associated

neoplasia. Pathol Res Pract. 2020;216: 152972.

18. Preston SL, Leedham SJ, Oukrif D, et al. The development of

duodenal microadenomas in FAP patients: the human correlate of

the min mouse. J Pathol. 2008;214:294–301.

19. Quan L, Ohgaki R, Hara S, et al. Amino acid transporter LAT1 in

tumor-associated vascular endothelium promotes angiogenesis by

regulating cell proliferation and VEGF-A-dependent mTORC1

activation. J Exp Clin Cancer Res. 2020;39:266.

20. Abremski K, Hoess R. Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. J Biol Chem. 1984;259:1509–14.

21. Ohgaki R, Ohmori T, Hara S, et al. Essential roles of L-type

amino acid transporter 1 in syncytiotrophoblast development by

presenting fusogenic 4F2hc. Mol Cell Biol. 2017;37:e00427e516.

J Gastroenterol (2023) 58:444–457

22. Barker N, Ridgway RA, van Es JH, et al. Crypt stem cells as the

cells-of-origin of intestinal cancer. Nature. 2009;457:608–11.

23. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal

integration to cancer, diabetes and ageing. Nat Rev Mol Cell

Biol. 2011;12:21–35.

24. Liu GY, Sabatini DM. Mtor at the nexus of nutrition, growth,

ageing and disease. Nat Rev Mol Cell Biol. 2020;21:183–203.

25. Alao JP. The regulation of cyclin D1 degradation: roles in cancer

development and the potential for therapeutic invention. Mol

Cancer. 2007;6:24.

26. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling:

components, mechanisms, and diseases. Dev Cell. 2009;17:9–26.

27. Rad E, Murray JT, Tee AR. Oncogenic signalling through

mechanistic target of rapamycin (mTOR): a driver of metabolic

transformation and cancer progression. Cancers (Basel).

2018;10:5.

28. Thoreen CC. The molecular basis of mTORC1-regulated translation. Biochem Soc Trans. 2017;45:213–21.

29. Thoreen CC, Chantranupong L, Keys HR, et al. A unifying model

for mTORC1-mediated regulation of mRNA translation. Nature.

2012;485:109–13.

30. Faller WJ, Jackson TJ, Knight JR, et al. mTORC1-mediated

translational elongation limits intestinal tumour initiation and

growth. Nature. 2015;517:497–500.

31. Kim C, Kim B. Anti-cancer natural products and their bioactive

compounds inducing ER stress-mediated apoptosis: a review.

Nutrients. 2018;10:1021.

32. Xu K, Han B, Bai Y, et al. MiR-451a suppressing BAP31 can

inhibit proliferation and increase apoptosis through inducing ER

stress in colorectal cancer. Cell Death Dis. 2019;10:152.

33. Zhang J, Xu Y, Li D, et al. Review of the correlation of LAT1

with diseases: mechanism and treatment. Front Chem. 2020;8:

564809.

34. Walsh JG, Cullen SP, Sheridan C, et al. Executioner caspase-3

and caspase-7 are functionally distinct proteases. Proc Natl Acad

Sci USA. 2008;105:12815–9.

35. Kitamura H, Ohno Y, Toyoshima Y, et al. Interleukin-6/STAT3

signaling as a promising target to improve the efficacy of cancer

immunotherapy. Cancer Sci. 2017;108:1947–52.

36. Huber S, Gagliani N, Zenewicz LA, et al. IL-22BP is regulated

by the inflammasome and modulates tumorigenesis in the intestine. Nature. 2012;491:259–63.

37. Popivanova BK, Kitamura K, Wu Y, et al. Blocking TNF-alpha

in mice reduces colorectal carcinogenesis associated with chronic

colitis. J Clin Investing. 2008;118:560–70.

457

38. Benito I, Encı´o IJ, Milagro FI, et al. Microencapsulated bifidobacterium bifidum and lactobacillus gasseri in combination

with quercetin inhibit colorectal cancer development in Apc(Min/

) mice. Int J Mol Sci. 2021;22:4906.

39. Bevins CL, Salzman NH. Paneth cells, antimicrobial peptides and

maintenance of intestinal homeostasis. Nat Rev Microbiol.

2011;9:356–68.

40. Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitute the

niche for Lgr5 stem cells in intestinal crypts. Nature.

2011;469:415–8.

41. Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build

crypt-villus structures in vitro without a mesenchymal niche.

Nature. 2009;459:262–5.

42. van der Flier LG, Haegebarth A, Stange DE, et al. OLFM4 is a

robust marker for stem cells in human intestine and marks a

subset of colorectal cancer cells. Gastroenterology.

2009;137:15–7.

43. Chen Q, Suzuki K, Sifuentes-Dominguez L, et al. Paneth cellderived growth factors support tumorigenesis in the small intestine. Life Sci Alliance. 2021;4: e202000934.

44. Farin HF, Van Es JH, Clevers H. Redundant sources of Wnt

regulate intestinal stem cells and promote formation of Paneth

cells. Gastroenterology. 2012;143:1518-29.e7.

45. Jewell JL, Russell RC, Guan KL. Amino acid signalling upstream

of mTOR. Nat Rev Mol Cell Biol. 2013;14:133–9.

46. Oshima M, Oshima H, Kitagawa K, et al. Loss of Apc

heterozygosity and abnormal tissue building in nascent intestinal

polyps in mice carrying a truncated Apc gene. Proc Natl Acad Sci

USA. 1995;92:4482–6.

47. Maiuri MC, Zalckvar E, Kimchi A, et al. Self-eating and selfkilling: crosstalk between autophagy and apoptosis. Nat Rev Mol

Cell Biol. 2007;8:741–52.

48. Najumudeen AK, Ceteci F, Fey SK, et al. The amino acid

transporter SLC7A5 is required for efficient growth of KRASmutant colorectal cancer. Nat Genet. 2021;53:16–26.

49. Kandasamy P, Gyimesi G, Kanai Y, et al. Amino acid transporters revisited: new views in health and disease. Trends Biochem Sci. 2018;43:752–89.

Publisher’s Note Springer Nature remains neutral with regard to

jurisdictional claims in published maps and institutional affiliations.

123

...

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る