Chunmei Guo

Past decade study of snake venom l-amino acid oxidase

As one of the major protein (enzyme) components of snake venom (SV), L-amino acid oxidase (LAAO) plays an important role in the toxicities and biological activities for SV. Accumulated researches in the past decade gradually revealed that SV-LAAOs induce platelet aggregation, cell apoptosis and cytotoxicity, and have anti-microbial, anti-leishmaniasis, anti-tumor and anti-HIV activity. Except for the enzymatic and structural characteristics of SV-LAAOs, the biological functions of SV-LAAOs and relevant action mechanisms are also summarized and discussed in the review. This work might provide useful inputs for future studies on SV-LAAOs.

The association of annexin A2 and cancers

Annexins are a group of calcium- and phospholipid-dependent proteins. As a member of the annexin, annexin A2 (Anxa2) is widely distributed in nucleus, cytoplasm and extracellular surface and mainly expressed in human endothelial cells, mononuclear cells, macrophages, marrow cells and some tumor cells. Accumulated evidences indicated that Anxa2 deregulation was associated with the occurrence, invasion and metastasis of cancers. Anxa2 up-regulation was related to the development, invasion, metastasis and drug resistance of hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, acute promyelocytic leukemia and renal cell carcinoma; while Anxa2 down-regulation was associated with prostate cancer, esophageal squamous carcinoma and nasopharyngeal carcinoma and sinonasal adenocarcinoma. The association between Anxa2 and malignant tumors as well as the potential action mechanisms were summarized in current work. Anxa2 might be used as a potential biomarker for the diagnosis, treatment and prognosis of certain tumors.

Novel insight into the role of GAPDH playing in tumor.

The role of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) being consistently regarded as the main housekeeping gene and reference gene/protein for expression quantification in tumors has been gradually questioned and challenged by accumulated experiment evidence. The current review notified that the GAPDH expression was deregulated in lung cancer, renal cancer, breast cancer, gastric cancer, glioma, liver cancer, colorectal cancer, melanoma, prostatic cancer, pancreatic cancer and bladder cancer. Interestingly, GAPDH was commonly up-regulated in a variety of types of cancer, which was revealed to be potentially required for the cancer cell growth and tumor formation. The relevant mechanisms were also discussed in current review. This work might provide useful insights for future studies on GAPDH in tumors.

Annexin A5 as a potential marker in tumors

Annexin A5 (Anxa5) promotes pancreatic adenocarcinoma, sarcoma, tumorigenesis and progression of breast cancer and prostate cancer stem cells. It is involved with metastasis, invasion and development of squamous cell carcinoma, and facilitates nodal progression of bladder cancer and angiogenesis and progression of glioma. Anxa5 de-regulation is associated with drug resistance in nasopharyngeal carcinoma and gastric cancer. Although Anxa5 protein up-regulation promotes cervical cancer progression, it is markedly suppressed in cervical carcinoma cells. Anxa5 is negatively correlated with thyroid cancer malignancy. In this review, we explore the mechanisms of Anxa5 action in tumors. Anxa5 could be a predictive biomarker for tumor development, metastasis and invasion, and be of diagnostic, prognostic and therapeutic significance in cancer.

Biochemical, functional and structural characterization of Akbu-LAAO: A novel snake venom L-amino acid oxidase from Agkistrodon blomhoffii ussurensis

An L-amino acid oxidase (Akbu-LAAO) was isolated from the venom of Agkistrodon blomhoffii ussurensis snake using DEAE Sephadex A-50 ion-exchange, Sephadex G-75 gel filtration, and high performance liquid chromatographies. The homogeneity and molecular mass of Akbu-LAAO were analyzed by SDS-PAGE and MALDI-TOF spectrometry. The sequences of ten peptides from Akbu-LAAO were established by HPLC-nESI-MS/MS analysis. Protein sequence alignment indicated that i) that Akbu-LAAO is a new snake venom LAAO, and ii) Akbu-LAAO shares homology with several LAAOs from the venoms of Calloselasma rhodost, Agkistrodon halys, Daboia russellii siamensis, and Trimeresurus stejnegeri. Akbu-LAAO is a homodimer with a molecular mass of approximately 124.4 kDa. It reacts optimally with its enzymatic substrate, Leu, at pH 4.7 with a K(m) of 2.1 mM. ICP-AES measurements showed that Akbu-LAAO contains four Zn(2+) per dimer that are unessential for the hydrolytic activity of the enzyme. The emission fluorescence intensity of Akbu-LAAO decreases by 61% on removal of Zn(2+) indicating that the zinc probably helps maintain the structural integrity of the enzyme. The addition of exogenous metal ions, including Mg(2+), Mn(2+), Ca(2+), Ce(3+), Nd(3+), Co(2+) and Tb(3+), increases the l-Leu hydrolytic activity of the enzyme. Akbu-LAAO shows apparent anti-aggregation effects on human and rabbit platelets. It exhibits a strong bacteriostasis effect on Staphylococcus aureus, eighteen fold that of cephalosporin C under the same conditions. Taken together, the biochemical, proteomic, structural and functional characterizations reveal that Akbu-LAAO is a novel LAAO with promise for biotechnological and medical applications.

Potential role of Anxa1 in cancer

The annexins are a well-known, closely related, multigene superfamily of Ca(2+)-regulated, phospholipid-dependent, membrane-binding proteins. As a member of the annexins, Anxa1 participates in a variety of important biological processes, such as cellular transduction, membrane aggregation, inflammation, phagocytosis, proliferation, differentiation and apoptosis. Accumulated evidence has indicated that Anxa1 deregulations are associated with the development, invasion, metastasis, occurrence and drug resistance of cancers. The research evidence in recent years indicates that Anxa1 might specifically function either as a tumor suppressor or a tumor promoter candidate for certain cancers depending on the particular type of tumor cells/tissues. This article summarizes the associations between Anxa1 and malignant tumors, as well as potential action mechanisms. Anxa1 has the potential to be used in the future as a biomarker for the diagnosis, treatment and prognosis of certain tumors.

The role of annexin A3 playing in cancers

Annexin family proteins are a well-known multigene family of Ca2+-regulated phospholipid- and membrane-binding proteins. As one of the annexin family genes/proteins, accumulated researches have begun to reveal that annexin A3 (Anxa3) exhibits important roles in tumor development, metastasis and drug resistance. The summarized research evidences in recent years indicate Anxa3 might specifically functionalize either as a tumor suppressor or as a tumor promoter candidate for different cancers depending on the types of tumor cells and tissues. The up-regulation of Anxa3 was found to be correlated with enhanced drug resistance of ovarian cancer, to promote the developments of colorectal adenocarcinoma and pancreatic carcinoma, and to facilitate the metastases of lung adenocarcinoma and hepatocarcinoma; meanwhile, the decreased Anxa3 expressions was negatively correlated with the developments of prostatic carcinoma and renal carcinoma. It is conceivable that Anxa3 could be regarded as a target for therapeutic intervention and a biological indicator for tumor development, invasion and metastasis as well as for the prognosis of tumor patients.

ACTB in cancer

Beta-actin (ACTB) has traditionally been regarded as an endogenous housekeeping gene and has been widely used as a reference gene/protein in quantifying expression levels in tumors. However, ACTB is closely associated with a variety of cancers and accumulating evidence indicates that ACTB is de-regulated in liver, melanoma, renal, colorectal, gastric, pancreatic, esophageal, lung, breast, prostate, ovarian cancers, leukemia and lymphoma. ACTB is generally found to be up-regulated in the majority of tumor cells and tissues. The abnormal expression and polymerization of ACTB and the resulting changes to the cytoskeleton are revealed to be associated with the invasiveness and metastasis of cancers. The current review explores relevant mechanisms, integrates current understandings, and provides suggestions for future studies of the roles of ACTB in tumors.

Potential role of annexin A7 in cancers.

Annexin A7 (Anxa7) is a member of the multigene annexin superfamily of Ca(2+)-regulated and phospholipid-binding proteins. Accumulated evidence indicates that the deregulation, loss of heterozygosity (LOH) and subcellular localization of Anxa7 are associated with the occurrence, invasion, metastasis and progression of a variety of cancers. Anxa7 appears to have a tumor-suppression role in glioblastoma, glioblastoma multiforme (GBM), melanoma and prostate cancer (CaP) but, controversially and interestingly, Anxa7 also appears to promote the development and malignancies of liver cancer, gastric cancer (GC), nasopharyngeal carcinoma (NPC), colorectal cancer (CRC) and breast cancer (BC). The associations between Anxa7 and malignant tumors as well as potential mechanisms of action are summarized and discussed in current review. Anxa7 has potential for use as a biomarker for the diagnosis, treatment and prognosis of certain tumors.

Annexin A4 and cancer.

Annexin A4 (Anxa4) is one of the Ca(2+)-regulated and phospholipid-binding annexin superfamily proteins. Anxa4 has a potential role in diagnosis, prognosis, and treatment of certain cancers. Studies indicate that Anxa4 up-regulation promotes the progression of tumor and chemoresistance of colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), endometrial carcinoma (EC), gastric cancer (GC), chemoresistant lung cancer (LC), malignant mesothelioma (MM), renal cell carcinoma (RCC), ovarian clear cell carcinoma (OCCC), cholangiocarcinoma, hepatocellular carcinoma (HCC), breast cancer (BC), and laryngeal cancer. Interestingly, Anxa4 also might specifically function as a tumor suppressor for prostate cancer (PCa) and have a paradoxical role for pancreatic cancer (PCC). Differential expression of Anxa4 may distinguish major salivary gland tumor (MSGT) from thyroid cancer. In addition, its differential expression was linked to Sirt1-induced cisplatin resistance of oral squamous cell carcinoma (OSCC) and miR-7-induced migration and invasion inhibition of glioma. This current review summarizes and discusses the clinical significance of Anxa4 in cancer as well as its potential mechanisms of action. It may provide new integrative understanding for future studies on the exact role of Anxa4 in cancer.