Lectin from Sambucus sieboldiana abrogates the anoikis resistance of colon cancer cells conferred by N-acetylglucosaminyltransferase V during hematogenous metastasis.

Anoikis is a form of anchorage-dependent apoptosis, and cancer cells adopt anokis-resistance molecular machinery to conduct metastasis. Here, we report that N-acetylglucosaminyltransferase V gene expression confers anoikis resistance during cancer progression. Overexpression of N-acetylglucosaminyltransferase V protected detached cancer cells from apoptotic death, and suppression or knockout of the gene sensitized cancer cells to the apoptotic death. The gene expression also stimulated anchorage-dependent as well as anchorage-independent colony formation of cancer cells following anoikis stress treatments. Importantly, treatment with the lectin from Sambucus sieboldiana significantly sensitized anoikis-induced cancer cell deaths in vitro as well as in vivo. We propose that the lectin alone or an engineered form could offer a new therapeutic treatment option for cancer patients with advanced tumors.

Directional Terahertz Radiation from GalnP Lateral Superlattice.

We devised directionally controllable THz emission sources based on lateral composition modulation (LCM) structures. LCM structures were composed of In-rich Ga0.47In0.53P and Ga-rich Ga0.51In0.49P layers whose period was in quantum scale of ~`5 nm. The inherent type II band alignment in these structures leads to electron-hole (e-h) separation and plays a key role in generating later- ally polarized dipole ensembles, thus concomitantly emitting enhanced transmissive THz waves as compared to bulk sample. On the other hand, in lateral geometry, changes in THz fields between LCM and bulk structures turned out to negligible since the vertical electronic diffusion was allowed in both samples.

Polarized Terahertz Waves Emitted from In0.2Ga0.8As Nanowires.

We investigate the polarizability of terahertz (THz) waves emitted from undoped In0.2Ga0.8As nanowires (NWs). THz emission amplitude shows strong enhancement in vertically aligned NWs compared to less-aligned NWs. In particular, polarized THz waves are clearly demonstrated in aligned NWs via a drastic variation of amplitudes as a function of the axis angle in polarization-sensitive photoconductive antenna. In addition, phase reversal between aligned and less-aligned NWs substantiates the geometrical dependence of electronic diffusion in generating the transient THz electric fields.

PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site.

Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr(387) of Mst1. Yap1 was localized predominantly in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer.

N-Acetylglucosaminyltransferase V triggers overexpression of MT1-MMP and reinforces the invasive/metastatic potential of cancer cells.

N-Acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes the formation of a ß1,6-N-acetylglucosamine (GlcNAc) side chain to a core mannosyl residue in N-linked glycoproteins. Besides its direct function of producing aberrant glycoproteins, it promotes cancer progression by its involvement in the stimulation of oncoproteins. Herein, we report that GnT-V guided the transcriptional activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) in cancer cells. The activated MT1-MMP expression had dual effects on cancer progression. It not only promoted proteolytic activity for cancer cells per se, but also led to the activation of MMP-2. Consequently, the activation of the two MMPs triggered by GnT-V intensified the invasive potential. A quantitative analysis using clinical tissues revealed a relatively strong correlation between GnT-V overexpression and MT1-MMP upregulation. In this study, we report for the first time that GnT-V directs cancer progression by modulating MMPs in cancer.

Overexpression and ß-1,6-N-acetylglucosaminylation-initiated aberrant glycosylation of TIMP-1: a "double whammy" strategy in colon cancer progression.

There has been ongoing debate over whether tissue inhibitor of metalloproteinase-1 (TIMP-1) is pro- or anti-oncogenic. We confirmed that TIMP-1 reinforced cell proliferation in an αvß3 integrin-dependent manner and conferred resistance against cytotoxicity triggered by TNF-α and IL-2 in WiDr colon cancer cells. The cell-proliferative effects of TIMP-1 contributed to clonogenicity and tumor growth during the onset and early phase of tumor formation in vivo and in vitro. However, mass-produced TIMP-1 impeded further tumor growth by tightly inhibiting the activities of collagenases, which are critical for tumor growth and malignant transformation. Tumor cells could overcome this impasse by overexpression of N-acetylglucosaminyltransferase V, which deteriorates TIMP-1 into an aberrant glycoform. The aberrant glycoform of TIMP-1 was responsible for the mitigated inhibition of collagenases. The outbalanced activities of collagenases can degrade the basement membrane and the interstitial matrix, which act as a physical barrier for tumor growth and progression more efficiently. The concomitant overexpression of TIMP-1 and N-acetylglucosaminyltransferase V enabled WiDr cells to show a higher tumor growth rate as well as more malignant behaviors in a three-dimensional culture system.