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Cell Adhesion in Inflammation and Cancer

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DESCRIPTION OF LAB RESEARCH WORK
My lab investigates the molecular mechanisms of cell adhesion and migration underpinning normal and pathological conditions, including inflammation and cancer. We focus on two protein families – integrins and kindlins. Integrins are transmembrane protein heterodimers that mediate cell-cell, cell-extracellular matrix, and cell-virus interactions. A large number of cytosolic proteins have been identified to regulate integrin function. We seek to understand the molecular basis of cross-talks between these regulators of integrin function. One family of these regulators known as kindlins has emerged as key regulators of integrin activation and signaling. We have shown recently that kindlin-3 is important in leukemic cell proliferation. We are now examining the signaling network of kindlins and its contribution to cancer progression and drug resistance.

LAB MEMBERS
LEAD PI
Tan Suet Mien
Associate Professor

Email: smtan@ntu.edu.sg
Phone: (65) 6316 2634
Office: SBS-05N-10
Aye Sandi Bo ​
Project Officer

Email: sandybo@ntu.edu.sg
Carol Seah Huey Ying
Project Officer

Email: carolseah@ntu.edu.sg
Tan Hui Foon
PhD student

Email: S150006@e.ntu.edu.sg
Wong Jun Sheng
PhD Student

Email: s180053@e.ntu.edu.sg
Zarina Levitskaya
PhD Student

Email: zarina001@ntu.edu.sg

CURRENT PROJECTS
  • Examining a dual switch mechanism of integrin regulation by cytoskeletal protein filamin A in immune cells.

  • ​Developing a bi-molecular system to examine integrin clustering under normal and pathological conditions.

  • Investigating the role of kindlin-2 in mitotic spindle assembly in neuroblastoma cells.

  • Investigating the role of kindlin-3 in leukemic cell proliferation and drug resistance.



PUBLICATIONS
  • Tan, H.F., and Tan, S.M. (2020) The focal adhesion protein kindlin-2 controls mitotic spindle assembly by inhibiting histone deacetylase 6 and maintaining α-tubulin acetylation. J. Biol. Chem. 295, 5928-5943.

  • Bu. W.T., Levitskaya, Z., Loh, Z. Y., Jin, S., Basu, S., Ero, R., Yan, X., Wang, M., Sze, S.K., Tan, S.M.*, and Gao, Y.G*. (2020) Structural basis of human full-length kindlin-3 homotrimer in an auto-inhibited state. PLOS Bio. 18(7):e3000755 *co-correspondence.

  • Guan, S.Y., Chng, C.P., Ong, L.T., Tan, H.F., Law, S.K.A., and Tan, S.M. (2018) The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK. FEBS Lett, 592, 112-121.

  • Chatterjee, D., D’Souza, A., Zhang, Y., Bin W., Tan, S.M., and Bhattacharjya, S. (2018) Interaction analyses of 14-3-3ζ, Dok1, and phosphorylated integrin β cytoplasmic tails reveal a bi-molecular switch in integrin regulation. J. Mol. Biol. 430, 4419-4430. *co-correspondance

  • Chatterjee, D., Lewis Lu Z.P., Tan, S.M.*, and Bhattacharya, S.* (2018) NMR Structure, Dynamics and Interactions of the Integrin β2 Cytoplasmic Tail with Filamin Domain IgFLNa21. Sci. Rep., 8, 5490. *co-correspondance.

  • Ong, L.T., Tan, H.F., Feng, C., Qu, J., Loh, S.C., Bhattachariya, S., and Tan, S.M. (2017) The Systemic Lupus Erythematosus associated single nucleotide polymorphism rs1143678 in integrin αM cytoplasmic tail generates a 14-3-3ζ binding site that is proinflammatory. J. Immunol. 198, 883-894.

  • Feng, C.*, Wee, W.K., Chen, H., Ong, L.T., Qu, J., Tan, H.F., and Tan, S.M. (2016) Expression of kindlin-3 in melanoma cells impedes cell migration and metastasis. Cell Adh Migr. 7, 1-15.

  • Chatterjee, D., Zhiping, L.L., Tan, S.M.*, and Bhattacharjya, S.* (2016) Interaction analyses of the integrin β2 cytoplasmic tail with the F3 FERM domain of talin and 14-3-3ζ reveal a ternary complex with phosphorylated tail. J. Mol. Biol. 428, 4129-4142. *co-corresponding authors.

  • Qu, J., Ero, R., Feng, C., Ong, L.T., Tan, H.F., Lee, H.S., Ismail, M.H., Bu, W.T., Nama, S., Sampath, P., Gao, Y.G., and Tan, S.M. (2015) Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells. Sci. Rep. 5:18491.

  • Feng, C., Li, Y.F., Yau, Y.H., Lee, H.S., Tang, X.Y., Xue, Z.H., Zhou, Y.C., Lim, W.M., Cornvik, T.C., Ruedl, C., Shochat, S.G., and Tan, S.M. (2012) Kindlin-3 mediates integrin αLß2 outside-in signaling and it interacts with the scaffold protein receptor for activated-C kinase (RACK1). J. Biol. Chem. 287, 10714-10725 (selected for Faculty of 1000 Biology, 2012)

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