Integrin Beta8 (ITGB8) Activates VAV-RAC1 Signaling Via FAK in the Acquisition of Endometrial Epithelial Cell Receptivity for Blastocyst Implantation

Overview

Journal Sci Rep

Specialty Science

Date 2017 May 17

PMID 28507287

Citations 14

Authors

Vijay Kumar

Upendra Kumar Soni

Vineet Kumar Maurya

Kiran Singh

Rajesh Kumar Jha

Affiliations

Soon will be listed here.

Abstract

Integrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst first interacts with the luminal endometrial epithelial cells during its implantation; therefore, we have investigated the signaling of ITGB8 via FAK and VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5, 0500 h) stages of endometrial receptivity period in the mouse. Integrins downstream molecule FAK has demonstrated an increased expression and phosphorylation (Y397) in the endometrium as well as in the isolated endometrial epithelial cells during receptive and post-receptive stages. Integrin beta8 can functionally interact with FAK, VAV and RAC1 as the levels of phosphorylated-FAK, and VAV along with the RAC-GTP form was reduced after ITGB8 knockdown in the endometrial epithelial cells and uterus. Further, VAV and RAC1 were seen poorly active in the absence of FAK activity, suggesting a crosstalk of ITGB8 and FAK for VAV and RAC1 activation in the endometrial epithelial cells. Silencing of ITGB8 expression and inhibition of FAK activity in the Ishikawa cells rendered poor attachment of JAr spheroids. In conclusion, ITGB8 activates VAV-RAC1 signaling axis via FAK to facilitate the endometrial epithelial cell receptivity for the attachment of blastocyst.

Citing Articles

MYO6 contributes to tumor progression and enzalutamide resistance in castration-resistant prostate cancer by activating the focal adhesion signaling pathway.

Zheng S, Hong Z, Tan Y, Wang Y, Li J, Zhang Z Cell Commun Signal. 2024; 22(1):517.

PMID: 39449086 PMC: 11515482. DOI: 10.1186/s12964-024-01897-z.

The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways.

Mafi A, Hedayati N, Kahkesh S, Khoshayand S, Alimohammadi M, Farahani N Noncoding RNA Res. 2024; 9(4):1178-1189.

PMID: 39022676 PMC: 11250881. DOI: 10.1016/j.ncrna.2024.05.010.

Dichotomous transactivation domains contribute to growth inhibitory and promotion functions of TAp73.

Li D, Kok C, Wang C, Ray D, Osterburg S, Dotsch V Proc Natl Acad Sci U S A. 2024; 121(21):e2318591121.

PMID: 38739802 PMC: 11127001. DOI: 10.1073/pnas.2318591121.

Functional Conservation of the Small GTPase Rho5/Rac1-A Tale of Yeast and Men.

Bischof L, Schweitzer F, Heinisch J Cells. 2024; 13(6.

PMID: 38534316 PMC: 10969153. DOI: 10.3390/cells13060472.

Pericardial delta like non-canonical NOTCH ligand 1 (Dlk1) augments fibrosis in the heart through epithelial to mesenchymal transition.

Jensen C, Johnsen R, Eskildsen T, Baun C, Ellman D, Fang S Clin Transl Med. 2024; 14(2):e1565.

PMID: 38328889 PMC: 10851088. DOI: 10.1002/ctm2.1565.

References

Chadchan S, Kumar V, Maurya V, Soni U, Jha R . Endoglin (CD105) coordinates the process of endometrial receptivity for embryo implantation. Mol Cell Endocrinol. 2016; 425:69-83. DOI: 10.1016/j.mce.2016.01.014. View

Shen T, Park A, Alcaraz A, Peng X, Jang I, Koni P . Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol. 2005; 169(6):941-52. PMC: 2171636. DOI: 10.1083/jcb.200411155. View

P F Nader G, Ezratty E, Gundersen G . FAK, talin and PIPKIγ regulate endocytosed integrin activation to polarize focal adhesion assembly. Nat Cell Biol. 2016; 18(5):491-503. DOI: 10.1038/ncb3333. View

Li Y, Sun X, Dey S . Entosis allows timely elimination of the luminal epithelial barrier for embryo implantation. Cell Rep. 2015; 11(3):358-65. PMC: 5089169. DOI: 10.1016/j.celrep.2015.03.035. View

Png F, Murphy C . Cytoskeletal proteins in uterine epithelial cells only partially return to the pre-receptive state after the period of receptivity. Acta Histochem. 2002; 104(3):235-44. DOI: 10.1078/0065-1281-00652. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Riemenschneider M, Mueller W, Betensky R, Mohapatra G, Louis D . In situ analysis of integrin and growth factor receptor signaling pathways in human glioblastomas suggests overlapping relationships with focal adhesion kinase activation. Am J Pathol. 2005; 167(5):1379-87. PMC: 1603783. DOI: 10.1016/S0002-9440(10)61225-4. View

Zhang L, Rees M, Bicknell R . The isolation and long-term culture of normal human endometrial epithelium and stroma. Expression of mRNAs for angiogenic polypeptides basally and on oestrogen and progesterone challenges. J Cell Sci. 1995; 108 ( Pt 1):323-31. DOI: 10.1242/jcs.108.1.323. View

Choma D, Milano V, Pumiglia K, DiPersio C . Integrin alpha3beta1-dependent activation of FAK/Src regulates Rac1-mediated keratinocyte polarization on laminin-5. J Invest Dermatol. 2006; 127(1):31-40. DOI: 10.1038/sj.jid.5700505. View

10.

Tranguch S, Daikoku T, Guo Y, Wang H, Dey S . Molecular complexity in establishing uterine receptivity and implantation. Cell Mol Life Sci. 2005; 62(17):1964-73. PMC: 11139181. DOI: 10.1007/s00018-005-5230-0. View

11.

Green C, Fraser S, Day M . Insulin-like growth factor 1 increases apical fibronectin in blastocysts to increase blastocyst attachment to endometrial epithelial cells in vitro. Hum Reprod. 2014; 30(2):284-98. DOI: 10.1093/humrep/deu309. View

12.

Vuori K . Integrin signaling: tyrosine phosphorylation events in focal adhesions. J Membr Biol. 1998; 165(3):191-9. DOI: 10.1007/s002329900433. View

13.

Mitra S, Mikolon D, Molina J, Hsia D, HANSON D, Chi A . Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors. Oncogene. 2006; 25(44):5969-84. DOI: 10.1038/sj.onc.1209588. View

14.

Wang J, Armant D . Integrin-mediated adhesion and signaling during blastocyst implantation. Cells Tissues Organs. 2002; 172(3):190-201. DOI: 10.1159/000066970. View

15.

Hanks S, Ryzhova L, Shin N, Brabek J . Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front Biosci. 2003; 8:d982-96. DOI: 10.2741/1114. View

16.

Kaneko Y, Lecce L, Murphy C . Ovarian hormones regulate expression of the focal adhesion proteins, talin and paxillin, in rat uterine luminal but not glandular epithelial cells. Histochem Cell Biol. 2009; 132(6):613-22. DOI: 10.1007/s00418-009-0641-x. View

17.

Movilla N, Dosil M, Zheng Y, Bustelo X . How Vav proteins discriminate the GTPases Rac1 and RhoA from Cdc42. Oncogene. 2002; 20(56):8057-65. DOI: 10.1038/sj.onc.1205000. View

18.

Tu Z, Wang Q, Cui T, Wang J, Ran H, Bao H . Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice. Cell Death Differ. 2015; 23(1):169-81. PMC: 4815987. DOI: 10.1038/cdd.2015.98. View

19.

Kaneko Y, Lecce L, Day M, Murphy C . β(1) and β(3) integrins disassemble from basal focal adhesions and β(3) integrin is later localised to the apical plasma membrane of rat uterine luminal epithelial cells at the time of implantation. Reprod Fertil Dev. 2011; 23(3):481-95. DOI: 10.1071/RD10211. View

20.

Kang Y, Forbes K, Carver J, Aplin J . The role of the osteopontin-integrin αvβ3 interaction at implantation: functional analysis using three different in vitro models. Hum Reprod. 2014; 29(4):739-49. DOI: 10.1093/humrep/det433. View