doi:10.1093/jmcb/mjv024
Journal of Molecular Cell Biology (2015), 7(2), 91
| 91
Editorial
New insights into the regulation of tumorigenesis
As a highly complex disease, cancer has been exten-
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China E-mail: [email protected]
underlying the regulation of cell proliferation by tumor suppressors. It is known that a large proportion of human breast cancer cases are initially estrogen-dependent. Estrogen receptor a (ERa) is expressed in 75% of human breast cancer and the ER pathway participates in the developmental processes of breast cancer. In this issue, Dr Chiocca’s laboratory reported that the mitogen-triggered phosphorylation of histone deacetylase 1 (HDAC1), which is an important epigenetic factor to regulate chromatin structure, was mediated by PI3K/mTOR pathway through activating the p70 S6 kinase (S6K1) in breast cancer cells. Such S6K1 activation was required to drive the mTOR-mediated, HDAC1-dependent transcriptional control of ERa expression, indicating a novel cross-talk between the HDAC1 and PI3K pathways. The extracellular environment around tumor cells is important to influence tumor development. In this issue, Dr Klemm’s group and collaborators reported that tumor-derived microvesicles (T-MV) could directly promote the tumor cell invasion in a both autologous and heterologous manner. The authors identified that the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) was a biomarker for proinvasive MV, with high expression levels on MV from metastatic breast cancer patients. The authors finally concluded that T-MV-induced cancer cell invasion is mediated by highly glycosylated EMMPRIN through activation of the p38/MAPK signaling pathway, without affecting MMPs, in the tumor cells.
References Wu, J. (2013a). New way to tumor therapeutics. J. Mol. Cell Biol. 5, 1 – 2. Wu, J. (2013b). DNA damage and tumorigenesis. J. Mol. Cell Biol. 5, 155 –156.
# The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
Downloaded from http://jmcb.oxfordjournals.org/ by guest on November 17, 2015
Editor-in-Chief Jiarui Wu
sively analyzed by classical experimental biology assays and Omics approaches. Previously, we have published many papers as well as two collections of JMCB in the area of cancer biology (Wu, 2013a, b). The collection of research articles in this issue further reveals various regulating mechanisms of tumorigenesis, which might contribute to the discovery of new drug targets or therapeutic strategies. The main function of most tumor suppressors such as p53 is to regulate cell cycle. Two articles in this issue report new data on this topic. Dr Li’s group and collaborators uncovered a novel aspect of the functional interaction between p53 and Smad1. They found that Smad1 was upregulated in p53-deficient tumor samples. Knockdown of the elevated Smad1 in p532/2 MEFs resulted in an increase in cell proliferation, E1A/Ras-induced cell transformation, and tumorigenesis, which might be mediated through p57Kip2 expression and Atm – Chk2 signaling. They also showed that the elevated Smad1 generated chemoresistance in colorectal cancers. This work suggests that Smad1 elevation serves as a compensatory mechanism for p53 deficiency, and Smad1 plays critical roles in both tumor suppression and chemosensitivity. In another work, Dr Howitt and colleagues reported that the spatial distribution and signaling specificity of Pten, another important tumor suppressor, were regulated by Ndfip1. The authors showed that knockdown of Ndfip1 resulted in a loss of Pten nuclear compartmentalization and increased cell proliferation, whereas cytoplasmic Pten remained unaffected and active in regulating PI3K/Akt signaling. They further showed that cells lacking nuclear Pten had dysregulated expressions of two oncogenic proteins, Plk1 and cyclin D1. Taken together, these findings provide novel molecular mechanisms
Journal of Molecular Cell Biology (2015), 7(2), 91
| 91
Editorial
New insights into the regulation of tumorigenesis
As a highly complex disease, cancer has been exten-
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China E-mail: [email protected]
underlying the regulation of cell proliferation by tumor suppressors. It is known that a large proportion of human breast cancer cases are initially estrogen-dependent. Estrogen receptor a (ERa) is expressed in 75% of human breast cancer and the ER pathway participates in the developmental processes of breast cancer. In this issue, Dr Chiocca’s laboratory reported that the mitogen-triggered phosphorylation of histone deacetylase 1 (HDAC1), which is an important epigenetic factor to regulate chromatin structure, was mediated by PI3K/mTOR pathway through activating the p70 S6 kinase (S6K1) in breast cancer cells. Such S6K1 activation was required to drive the mTOR-mediated, HDAC1-dependent transcriptional control of ERa expression, indicating a novel cross-talk between the HDAC1 and PI3K pathways. The extracellular environment around tumor cells is important to influence tumor development. In this issue, Dr Klemm’s group and collaborators reported that tumor-derived microvesicles (T-MV) could directly promote the tumor cell invasion in a both autologous and heterologous manner. The authors identified that the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) was a biomarker for proinvasive MV, with high expression levels on MV from metastatic breast cancer patients. The authors finally concluded that T-MV-induced cancer cell invasion is mediated by highly glycosylated EMMPRIN through activation of the p38/MAPK signaling pathway, without affecting MMPs, in the tumor cells.
References Wu, J. (2013a). New way to tumor therapeutics. J. Mol. Cell Biol. 5, 1 – 2. Wu, J. (2013b). DNA damage and tumorigenesis. J. Mol. Cell Biol. 5, 155 –156.
# The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
Downloaded from http://jmcb.oxfordjournals.org/ by guest on November 17, 2015
Editor-in-Chief Jiarui Wu
sively analyzed by classical experimental biology assays and Omics approaches. Previously, we have published many papers as well as two collections of JMCB in the area of cancer biology (Wu, 2013a, b). The collection of research articles in this issue further reveals various regulating mechanisms of tumorigenesis, which might contribute to the discovery of new drug targets or therapeutic strategies. The main function of most tumor suppressors such as p53 is to regulate cell cycle. Two articles in this issue report new data on this topic. Dr Li’s group and collaborators uncovered a novel aspect of the functional interaction between p53 and Smad1. They found that Smad1 was upregulated in p53-deficient tumor samples. Knockdown of the elevated Smad1 in p532/2 MEFs resulted in an increase in cell proliferation, E1A/Ras-induced cell transformation, and tumorigenesis, which might be mediated through p57Kip2 expression and Atm – Chk2 signaling. They also showed that the elevated Smad1 generated chemoresistance in colorectal cancers. This work suggests that Smad1 elevation serves as a compensatory mechanism for p53 deficiency, and Smad1 plays critical roles in both tumor suppression and chemosensitivity. In another work, Dr Howitt and colleagues reported that the spatial distribution and signaling specificity of Pten, another important tumor suppressor, were regulated by Ndfip1. The authors showed that knockdown of Ndfip1 resulted in a loss of Pten nuclear compartmentalization and increased cell proliferation, whereas cytoplasmic Pten remained unaffected and active in regulating PI3K/Akt signaling. They further showed that cells lacking nuclear Pten had dysregulated expressions of two oncogenic proteins, Plk1 and cyclin D1. Taken together, these findings provide novel molecular mechanisms
