O ver the last few years there has been increasing interest in the matrix metalloproteinases (MMPs) in asthma. The MMPs are a family of over 20 zinc dependent endopeptidases with a range of substrate specificities. Although originally classified into gelatinases, stromolysins, collagenases, and matrilysins by their ability to cleave extracellular matrix components, it is now clear that MMPs hav...

Tumor suppressor SMAR1 interacts and stabilizes p53 through phosphorylation at its serine-15 residue. We show that SMAR1 transcription is regulated by p53 through its response element present in the SMAR1 promoter. Upon Doxorubicin induced DNA damage, acetylated p53 is recruited on SMAR1 promoter that allows activation of its transcription. Once SMAR1 is induced, cell cycle arrest is observed t...

Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer due to chronic inflammation. In IBD, chronic inflammation relies upon a TGFb signaling blockade, but its precise mechanistic relationship to colitis-associated colorectal cancer (CAC) remains unclear. In this study, we investigated the role of the TGFb signaling inhibitor Smad7 in CAC pathogene...

The normal differentiation of follicles from the preantral to the antral stage is regulated by the synthesis and secretion of several important growth factors. Moreover, the proper growth and development of the oocyte and its surrounding somatic granulosa-cumulus cells is accomplished through the activation of paracrine pathways that form a specific cross-talk between the gamete and somatic cel...

The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression of HMGA2 in epithelial cells induces epithelial–mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known about in vi...

The impact of complement on cancer metastasis has not been well studied. In this report, we demonstrate in a preclinical mouse model of breast cancer that the complement anaphylatoxin C5a receptor (C5aR) facilitates metastasis by suppressing effector CD8þ and CD4þT-cell responses in the lungs.Mechanisms of this suppression involve recruitment of immature myeloid cells to the lungs and regulatio...

Cancer stem-like cells contribute to tumor heterogeneity and have been implicated in disease relapse and drug resistance. Here we show the coexistence of distinct breast cancer stem-like cells (BCSC) as identified by ALDHþ and CD29hiCD61þ markers, respectively, in murine models of breast cancer. While both BCSC exhibit enhanced tumor-initiating potential, CD29hiCD61þ BCSC displayed increased in...

nant type I receptor in vitro (references can be found The transforming growth factor b (TGFb) family of cytoin Massagué and Weis-Garcia, 1996). Phosphorylation kines regulates cell proliferation, differentiation, recogoccurs in a cluster of five serine and threonine residues nition, and death and figures prominently in the control in the GS domain, a highly conserved region next to the of deve...

Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate...

The potential role of transforming growth factor-p (TGFB) as a mediator of cell-cell interactions during the pubertal development of the seminiferous tubule was examined. Mesenchymal-derived peritubular cells and epithelial-like Sertoli cells were isolated from prepubertal, midpubertal, and late pubertal rat testes. The developmental expression of the multiple forms of TGFB (TGFPl, -82, and -83...