Low LATS2 mRNA level can predict favorable response to epirubicin plus cyclophosphamide, but not to docetaxel, in breast cancers

Miyoshi, Yasuo; Taguchi, Tetsuya; Tamaki, Yasuhiro; Noguchi, Shinzaburo

doi:10.1007/s00432-007-0194-0

Cited by 21 publications

(19 citation statements)

References 44 publications

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“…However, in this study, only implicated in soft tissue sarcomas, leukemia, astrocytoma and in cancers of the breast, prostate, lung, liver and esophagus. [2][3][4][5][6][7][8][9][10] Decreased expression of LATS2 is seen in prostate cancer tissues, 7 and levels of phosphorylated LATS1/LATS2 are reduced in tumor susceptible mst1/2 liver-specific knockout mice. 9 Classically, tumor suppressor loss-of-function occurs through mutations.…”

Section: Role Of Lats As Tumor Suppressormentioning

confidence: 99%

“…As such, loss of either of these genes leads to malignant phenotypes. [2][3][4][5][6][7][8][9][10] Therefore, understanding how LATS1 and LATS2 operate is key to understanding tumorigenesis. This review will explore what we know about how these tumor suppressors function, both as individual proteins and collectively, highlighting their potential redundant or distinct roles.…”

Section: A New Governor Of Cellular Homeostasismentioning

confidence: 99%

“…In one study, patients with low LATS2 expression were significantly more likely to respond positively to etoposide plus cyclophosphamide (EC) treatment, whereas low levels of LATS1 were also associated, but not significantly, with better response rates to EC treatment. Importantly, neither LATS1 nor LATS2 levels showed any significant association with response rates to docetaxel (DOC), 6 suggesting that levels of LATS expression, particularly LATS2, can be used to determine treatment options for breast cancer patients.…”

Section: Cip1mentioning

confidence: 99%

See 2 more Smart Citations

LATS tumor suppressor: A new governor of cellular homeostasis

Visser

Yang²

2010

Cell Cycle

183

197

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Section: Role Of Lats As Tumor Suppressormentioning

confidence: 99%

Section: A New Governor Of Cellular Homeostasismentioning

confidence: 99%

Section: Cip1mentioning

confidence: 99%

See 1 more Smart Citation

LATS tumor suppressor: A new governor of cellular homeostasis

Visser

Yang²

2010

Cell Cycle

183

197

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“…Furthermore, mutations or reduced levels of LATS1 and/or LATS2 mRNAs or proteins have been found in a variety of human cancers including breast and prostate cancers, astrocytomas, acute lymphoblastic leukemia, and soft tissue sarcomas [33][34][35][36][37]. Recently, LATS1 levels are also used as a prognostic factor in predicting the outcome for node-positive breast cancer patients, while LATS2 levels have been used in predicting the response of breast cancer patients to selective chemotherapy [36,38].…”

Section: Lats In Cancermentioning

confidence: 99%

“…Furthermore, hMOB1 may also be a prognostic factor for predicting tumor development similar to LATS1 which is a prognostic factor for breast cancer and LATS2, a predictor for treatment in breast cancer [36,38]. A more detailed study of the human MOB family regulation at the molecular level will be essential to fully understand the role of this family in cancer development.…”

Section: Future Directionsmentioning

confidence: 99%

Molecular characterization of human homologs of yeast MOB1

Chow

Hao

Yang

2009

Intl Journal of Cancer

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MOB (Mps One Binder) is a conserved gene family found in all major kingdoms.The MOB genes are essential components acting in mitotic exit and cytokinesis in both budding and fission yeasts. They are further identified as tumor suppressors in Drosophila (D.) melanogaster. Recently, they are found to be involved in the emerging Drosophila Hippo-LATS tumor suppressor pathway. Seven human homologs of yeast MOB (hMOB1A, 1B, 2A, 2B,3,4,5) have been discovered. The hMOB1B is the gene that has been extensively studied and is reported to be required for the activation of LATS (Large Tumor Suppressor)/NDR (Nuclear Dbf2-related) protein kinase family, however, the functional significance of the gene remains unknown. This study is the first to elucidate the biological and biochemical functions of all seven human MOBs. By examining hMOB mRNA expression in various human tissues, we found that the hMOBs have exhibited different expression patterns. We also investigated the subcellular localization of hMOBs during interphase through immunofluorescent analysis. While hMOB2A is localized in the cytoplasm, hMOB4 is exclusively found in the nucleus. All of the other hMOBs are localized in both cytoplasm and nucleus. Furthermore, we identified hMOB1A and hMOB1B as the main binding partners of LATS and NDR in vitro. Additionally, we successfully identified a region on hMOB1B for the interaction with LATS or NDR and determined the crucial residue that is responsible for the binding of LATS2 with hMOB1B. Most significantly, we found that over-expression of hMOB1B in human cancer cells inhibits cell proliferation and induces cell death.Moreover, hMOB1B when targeted to the plasma membrane dramatically enhances the iii phenotype. Conversely, small interfering (si) RNA-mediated suppression of either endogenous hMOB1A or hMOB1B causes increased cell proliferation, whereas suppression of both hMOB1A and hMOB1B demonstrates a more significant enhancement in tumor cell growth. Moreover, co-expression of both LATS and hMOB1B targeted to the plasma membrane completely abolishes cell proliferation. Our findings provide convincing evidence that hMOB1A and hMOB1B function as negative regulators of cell proliferation and as pro-apoptotic proteins. Understanding hMOBs functions in the cell and their possible role in tumorigenesis can provide important information for the diagnosis and treatment of human cancers.iv ACKNOWLEDGEMENTS

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The Hippo pathway in chemotherapeutic drug resistance

Zhao

Yang

2014

Intl Journal of Cancer

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Chemotherapy is one of the major treatments for cancer patients. Although chemotherapeutic drugs can sometimes effectively suppress tumor growth in cancer patients, a significant proportion of patients are either intrinsically resistant or later develop resistance to primary chemotherapy, leading to disease relapse and patient mortality. The best way to conquer the resistance is the better understanding of the molecular network in cancer cells in response to drugs. Therefore, identification of signaling pathways and molecules involved in drug resistance is essential for successful treatment of cancers. The Hippo pathway is an emerging signaling pathway that plays important roles in tumorigenesis, stem cell self‐renewal and differentiation, organ size control as well as many other biological processes. Therefore, exploring novel roles of the Hippo pathway in various biological functions has become one of the cutting‐edge research areas in cancer and other biomedical research. Recently, we and others have provided new evidence that the Hippo pathway is involved in the resistance of different types of cancer cells to various chemotherapeutic drugs. In this review, we will discuss the specific roles of the Hippo pathway in chemotherapy, potential applications for studying this network in response to drugs as well as the future direction in identification of therapeutic targets.

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Low LATS2 mRNA level can predict favorable response to epirubicin plus cyclophosphamide, but not to docetaxel, in breast cancers

Cited by 21 publications

References 44 publications

LATS tumor suppressor: A new governor of cellular homeostasis

LATS tumor suppressor: A new governor of cellular homeostasis

Molecular characterization of human homologs of yeast MOB1

The Hippo pathway in chemotherapeutic drug resistance

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