Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia

Huang, Dan; Yang, Yan; Sun, Jian; Dong, Xiao-Rong; Wang, Jiao; Liu, Hongchen; Chen, Lu; Chen, Xueyu; Shao, Jing; Yan, Jinsong

doi:10.1007/s11684-017-0527-6

Cited by 29 publications

(38 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The proteins 14-3-3 ζ/δ and Ezrin, which link cytoskeletal and membrane proteins, have also implicated in cellular movement contributing to tumorigenesis, invasion, and metastasis (33, 34). Two Annexin A2 monomers bridged by an S100A10 homodimer are known to form a multifunctional membrane-associated heterotetramer (35), which has been implicated in membrane trafficking events and membrane-cytoskeletal connection relating to cell motility and drug-resistance in human cancers (36,37). S100A10, a small dimeric helix-loop-helix protein residing in a tight complex with Annexin A2, appeared to regulate the intracellular trafficking of a variety of membrane-resident proteins, such as cathepsin B (38).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms by Which S100A4 Regulates the Migration and Invasion of PGCCs With Their Daughter Cells in Human Colorectal Cancer

Fei

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Recently, an increasing number of evidences have shown that polyploid giant cancer cells (PGCCs) could generate daughter cells with a strong migration and invasion ability, which have been implicated in cancer recurrence and metastasis. However, the underlying molecular mechanisms of PGCCs with their daughter cells remain largely unclear. In vitro and in vivo experiments combined with 222 cases of human colorectal cancer (CRC) samples were used to identify the molecular mechanisms of S100A4-related proteins regulating the invasion and metastasis of PGCCs with their daughter cells. PGCCs with their daughter cells had high migration, invasion, and proliferation abilities compared to control cells; these were significantly inhibited after S100A4 knockdown. The high expression of cathepsin B, cyclin B1, TRIM21, and Annexin A2 were significantly downregulated after S100A4 knockdown, while the overexpression of S100A4, cathepsin B, cyclin B1, and S100A10 were significantly downregulated after TRIM21 knockdown in PGCCs with their daughter cells. The tumorigenic and metastatic ability of PGCCs with their daughter cells in vivo was significantly stronger compared to the untreated cells, which was significantly decreased after S100A4 knockdown. Moreover, the expression of S100A4-related proteins was positively correlated with the malignancy degree of human CRC, and maintained a high level in lymph node metastasis. S100A4 and TRIM21 may regulate each other to affect the expression and subcellular localization of cyclin B1, and participate in regulating the structure and function of Annexin A2/S100A10 complex, affecting downstream cathepsin B, resulting in the invasion and metastasis of PGCCs with their daughter cells. Besides, 14-3-3 ζ/δ and Ezrin may be involved in the motility and invasion of PGCCs with their daughter cells via cytoskeletal constructions with S100A4.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms by Which S100A4 Regulates the Migration and Invasion of PGCCs With Their Daughter Cells in Human Colorectal Cancer

Fei

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…This expression of annexin A2 and S100A10, along with increase in AIIt, has been recently shown to be regulated both transcriptionally and translationally by PML/RARA. 70 Thus, degradation of PML/RARA by differentiating agents ATRA or ATO corrects these abnormalities in APL. The inhibitors of fibrinolysis are altered in APL.…”

Section: Increased Fibrinolysismentioning

confidence: 99%

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Kwaan

Weiss

Tallman

2019

Semin Thromb Hemost

View full text Add to dashboard Cite

Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.

show abstract

“…Also, p11 promotes invasiveness and metastasis of numerous cancers 6 – 9 via increased plasmin generation. P11 overexpression in cancers has been attributed to the presence of oncogenic RAS 7 and the promyelocytic leukemia-retinoic acid receptor-alpha (PML/RARα) oncogene present in acute promyelocytic leukemia (APL) 9 , 10 . Strategies to reduce p11 in cancer cells would be critical to block plasmin-dependent metastasis.…”

Section: Introductionmentioning

confidence: 99%

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆

et al. 2018

View full text Add to dashboard Cite

S100A10 (p11), a member of the S100 family of small dimeric EF-hand-type Ca2+-binding proteins, plays a role in a variety of both intracellular and extracellular processes. Previous studies have suggested that p11 is intrinsically unstable and requires binding to annexin A2 (p36) to prevent its rapid ubiquitylation and degradation. Our laboratory has shown that p11 levels are stimulated by the expression of the oncoprotein, PML/RARα. Furthermore, treatment of the APL cell line, NB4 with all-trans retinoic acid (ATRA) causes the rapid loss of p36 and p11 protein. However, the mechanism by which ATRA regulates p11 levels has not been established. Here, we show that the proteasomal inhibitor, lactacystin reversed the ATRA-dependent loss of p11, but did not cause an accumulation of ubiquitylated forms of p11, suggesting that ATRA promotes the proteasomal degradation of p11 in an ubiquitin-independent manner. ATRA treatment of MCF-7 breast cancer cells reduced p11 but not p36 transcript and protein levels, thus indicating that ATRA can regulate p11 levels independently of PML/RARα and p36. Overexpression of p36 upregulated p11 protein but not mRNA levels, indicating that p36 affects p11 post translationally. The forced expression of ubiquitin and p11 in 293 T cells resulted in ubiquitylation of p11 that was blocked by mutagenesis of lysine 57. This study highlights the complex regulation of p11 by retinoid signaling and challenges the hypothesis that ubiquitin-mediated proteasomal degradation of p11 represents a universal mechanism of regulation of this protein.

show abstract

Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia

Cited by 29 publications

References 35 publications

Molecular Mechanisms by Which S100A4 Regulates the Migration and Invasion of PGCCs With Their Daughter Cells in Human Colorectal Cancer

Molecular Mechanisms by Which S100A4 Regulates the Migration and Invasion of PGCCs With Their Daughter Cells in Human Colorectal Cancer

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆

Contact Info

Product

Resources

About