- BBSRB Rm B359, 741 South Limestone St.
University of North Carolina at Chapel Hill, 2003, Ph.D.
Our research interest is to understand the signaling mechanisms by which regulate cell migration and cancer metastasis. Cell migration, a key step in cancer invasion and metastasis, is a highly dynamic process that requires temporal and spatial regulation of integrin inactivation and focal adhesion disassembly. Focal adhesions (FAs, also called cell-matrix adhesions) are specific types of large macromolecular assemblies at the ventral surface of cells, functioning as both mechanical machineries and regulatory signaling hubs. During cell migration, nascent focal adhesions (also called focal complexes) are formed to stabilize lamellipodia at the front of cells while focal adhesions are disassembled at the trailing edges of cells. Focal adhesions have been clearly implicated in cancer metastasis. However, the molecular mechanisms that regulate focal adhesion dynamics and the role of focal adhesion dynamics in cancer metastasis remain to be elucidated.
The ubiquitin proteasome pathway regulates cell cycle, transcription and antigen processing, but its role in regulating cell adhesions and migration has just been recognized. In particular, our published and unpublished results have demonstrated the central role of the ubiquitin pathway in regulating focal adhesion dynamics and consequently cancer metastasis. The long-term goalof our lab is to identify novel ubiquitin pathways for cancer therapeutic approaches. Currently, we are focusing on identifying novel ubiquitin pathways that regulate cell adhesion dynamics, cell migration and cancer metastasis.
1. Huang C, Ni Y, Wang T, Gao Y, Haudenschild CC, Zhan X. Down-regulation of the filamentous actin cross-linking activity of cortactin by src-mediated tyrosine phosphorylation. J. Biol. Chem. 1997. 272:13911-13915.
2. Huang C, Tandon NN, Greco NJ, Ni Y, Wang T, Zhan X. Proteolysis of platelet cortactin by calpain. J. Biol. Chem. 1997. 272:19248-19252.
3. Huang C, Liu J, Haudenschild CC, Zhan X. The role of tyrosine phosphorylation of cortactin in the locmotion of endothelial cells. J. Biol. Chem. 1998. 273: 25770-25776.
4. Liu J. Huang C, Zhan X. Src is required for cell migration and shape changes induced by fibroblast growth factor 1. Oncogene 1999. 18:6700-6706.
5. Huang C, Rajfur Z, Borchers C, Shaller MD, Jacobson K. JNK phosphorylates paxillin and regulates cell migration. Nature. 2003, 424: 219-223. [PMID: 12853963]
6. Huang C, Borchers C, Shaller MD, Jacobson K Phosphorylation of paxillin by p38MARK is involved in NGF-induced neurite extension. J. Cell Biol. 2004. 164: 593-602. [PMID: 14970194]
7. Huang C, Jacobson K, Schaller MD. MAP kinases and cell migration. J. Cell. Sci. 2004. 117:4619-4628. [PMID: 15371522]
8. Huang C, Rajfur Z, Yousefi N, Chen Z, Jacobson K, Ginsberg MH. Talin Phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitination and cell migration. Nat Cell Biol. 2009, 11: 624-630. [PMID: 19363486]
9. Huang C. Roles of E3 ubiquitin ligases in cell adhesion and migration. Cell Adhesion and Migration 2010, 4: 9-18. [PMID: 20009572]
10. Huang C, Jacobson K. Detection of protein-protein interactions employing non-immune IgG and BirA-mediated biotinylation. BioTechniques, 2010, 49: 881-886. [PMID: 21143209]
11. Wu Z, Li X, Sunkara M, Spearman H, Morris AJ, Huang C. PIPKIgamma regulates focal adhesion dynamics and colon cancer cell invasion. PLoS One, 2011, 6: e24775. [PMID: 21931851]
12. Li X, Zhou Q, Sunkara M, Kutys M, Wu Z, Rychahou P, Morris AM, Zhu H, Evers BM, Huang C. Ubiquitination of PIPKIγ90 by HECTD1 regulates focal adhesion dynamics and cell migration. Journal of Cell Science, 2013, 126, 2617-2628.
13. Zheng Q, Li X, Sunkara M, Morris AJ, Wu W, Huang C. Leptin up-regulates HECTD1 to promote phosphoinositide metabolism and cell migration and invasion in breast cancer cells. J Pharmacol Clin Toxicol 2013, 1: 1001.
14 Wu T, Vander Kooi C, Shah P, Charnigo R, Huang C, Smyth SS, Morris AJ.
Integrin-mediated cell surface recruitment of autotaxin promotes persistent directional cell migration. FASEB J. 2014, 28, 861-870.
15 Deng S, Huang C. E3 ubiquitin ligases in regulating stress fiber, lamellipodium, and focal adhesion dynamics. Cell Adh Migr. 2014, 8, 49-54.
16 Jin J-K, Tien P-C , Cheng C-J, Song J, Huang C, Lin S-H Lin, Gallick GE. Talin1 S425 phosphorylation promotes prostate cancer bone metastasis through β1 integrin activation. Oncogene 34:1811-1821 (2015).
28. Xiang B, Zhang G, Ye S, Zhang R, Huang C, Liu J, Tao M, Ruan C, Susan S. Smyth SS, Sidney W. Whiteheart SW, Li Z. Characterization of a novel integrin binding protein that is important for platelet activation and in vivo thrombosis and hemostasis. Circulation 2015, 132: 2334-2344 (2015).
29. Qi L, Jafari N, Li X, Chen Z, Li L, Hytönen VP, Goult BT, Zhan C-G, and Huang C. Talin2-mediated traction force drives matrix degradation and cell invasion. J. Cell Sci. 129, 3661-3674 (2016).
30. Jafari N, Zheng Q, Li L, Qi L, Li W, Xiao J, Gao T, and Huang C. p70S6K1 (S6K1)-mediated phosphorylation regulates phosphatidylinositol 4-phosphate 5-kinase Type I γ degradation and cell invasion. J. Biol. Chem. 291: 25729-25741 (2016).
31. Jafari N, Kim H, Li L, Park R, Morris AJ, Park J, and Huang C. CRISPR-Cas9 mediated NOX4 knockout inhibits cell proliferation and invasion in HeLa cells. PLoS One, 12: e0170327 (2017).
32. Yuan Y, Li L, Zhu Y, Qi L, Azizi L, Hytönen VP, Zhan C-G, and Huang C. The molecular basis of talin2’s high affinity toward β1-integrin. Scientific Reports, 7: 41989 (2017).
33. Rahikainen R, von Essen M, Schaefer M, Qi L, Azizi L, Ihalainen T, Wehrle-Haller B, Bastmeyer M, Huang C, Hytönen V. Mechanical stability of talin rod controls traction force generation and cell migration. Scientific Reports, 7: 3571 (2017).