PTPL1: a large phosphatase with a split personality

Abaan, Ogan D.; Toretsky, Jeffrey A.

doi:10.1007/s10555-008-9114-2

Cited by 54 publications

(55 citation statements)

References 73 publications

(105 reference statements)

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“…Increased expression of miR-185 has also been observed in clear cell renal cell carcinoma compared to normal kidney tissues, and its expression is inversely correlated with its putative target PTPN13 (31). PTPN13 (protein tyrosine phosphatase, non-receptor type 13) is a Fas-associated protein tyrosine phosphatase and putative tumor suppressor gene that can inhibit PI3k/AkT signaling, suppress cell growth and induce apoptosis (32). Importantly, somatic PTPN13 mutations have been found in ~9% of CRCs (33), suggesting a critical role in the pathogenesis of CRC.…”

Section: Discussionmentioning

confidence: 99%

miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer

Akçakaya

Ekelund²,

Kolosenko³

et al. 2011

Int J Oncol

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Abstract. Colorectal cancer (CRC) is one of the most common and deadly forms of cancer. Despite improved treatment modalities, post-operative recurrence and metastasis remain the major problems for extending patient survival after surgery. This highlights the need to search for biomarkers for prognostication and treatment stratification of colorectal cancer patients. In this study, we applied the SYBR-green quantitative PCR-based array approach to screen for differentially expressed miRNAs between patients with short (<50 months, range 10-33 months) and long survival (≥50 months, range 50-152 months). The selected candidate prognostic miRNAs were validated in a cohort of 50 CRC patients by TaqMan quantitative PCR. We found that high expression of miR-185 and low expression of miR-133b were correlated with poor survival (p=0.001 and 0.028, respectively) and metastasis (p=0.007 and 0.036, respectively) in colorectal cancer. Our findings suggest the potential prognostic values of these miRNAs for predicting clinical outcome after surgery. IntroductionColorectal cancer (CRC) is the second most common cancer in women and the third in men worldwide (1). It ranks the second most common cause of cancer death in the Western world (2). Currently, there are several treatment modalities for CRC, including surgery, radiotherapy, chemotherapy and targeted therapy (e.g., cetuximab). However, the long-term survival remains low in metastatic disease (3).Given that CRC usually follows a stepwise progression from benign to malignant lesion and distant metastasis, there is a possibility for early diagnosis in order to reduce morbidity and mortality. The commonly used method to characterize CRC tumor in clinic is T1-T3 staging system. However, the staging system reflects only morphological characteristics of the tumor and does not consider tumor molecular biology, thus, it is inaccurate in predicting the future outcome for each particular case. Therefore, the development of screening tools and new biomarkers to facilitate early diagnosis is particularly warranted. Further investigations in the search for new prognostic biomarkers may help to improve post-operative treatment approaches for CRC patients.Several studies have documented a link between the aberrant expression of a class of small non-coding RNAs, termed microRNAs (miRNAs), and the pathogenesis/prognosis of several cancer types, including colorectal cancer (4,5). These molecules provide a potentially valuable diagnostic/prognostic tool for CRC pathology, because mature miRNA species are relatively more stable than mRNAs and well preserved in formalin-fixed, paraffin-embedded samples which are commonly used in clinical routine (6). Furthermore, only a small number of miRNAs are required to distinguish cancerous tissues from non-cancerous tissues compared with mRNA profiles (7), which makes them more feasible candidate biomarkers.miRNAs are endogenous single-stranded non-coding RNAs of ~22-nucleotides in length, which are generated by an RNase III enzyme Dicer from endogenou...

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Section: Discussionmentioning

confidence: 99%

miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer

Akçakaya

Ekelund²,

Kolosenko³

et al. 2011

Int J Oncol

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“…Involvement of PTPN13 in the Inhibitory Effect of Necl-2-It was reported that the protein-tyrosine phosphatase PTPN13 (also called PTPL1, FAP-1, PTP-BAS, and PTP1E), a known tumor suppressor (39), inhibits the ErbB2 activity by dephosphorylating the signal domain of ErbB2 and plays a role in attenuating the invasiveness and metastasis of ErbB2-overactive tumors (40). PTPN13 is a non-receptor type phosphatase with one FERM domain and five PDZ domains in addition to the catalytic domain (39).…”

Section: Involvement Of the Cytoplasmic Tail Of Necl-2 In Its Inhibitorymentioning

confidence: 99%

“…PTPN13 is a non-receptor type phosphatase with one FERM domain and five PDZ domains in addition to the catalytic domain (39). We therefore examined whether PTPN13 is responsible for the inhibitory effect of Necl-2 on the HRG-induced, ErbB2-catalyzed tyrosine phosphorylation of ErbB3.…”

Section: Involvement Of the Cytoplasmic Tail Of Necl-2 In Its Inhibitorymentioning

confidence: 99%

Silencing of ErbB3/ErbB2 Signaling by Immunoglobulin-like Necl-2

Kawano

Ikeda²,

Kishimoto

et al. 2009

Journal of Biological Chemistry

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ErbB2 and ErbB3, members of the EGF receptor/ErbB family, form a heterodimer upon binding of a ligand, inducing the activation of Rac small G protein and Akt protein kinase for cell movement and survival, respectively. The enhanced ErbB3/ ErbB2 signaling causes tumorigenesis, invasion, and metastasis. We found here that the ErbB3/ErbB2 signaling is regulated by immunoglobulin-like Necl-2, which is down-regulated in various cancer cells and serves as a tumor suppressor. The extracellular region of ErbB3, but not ErbB2, interacted in cis with that of Necl-2. This interaction reduced the ligand-induced, ErbB2-catalyzed tyrosine phosphorylation of ErbB3 and inhibited the consequent ErbB3-mediated activation of Rac and Akt, resulting in the inhibition of cancer cell movement and survival. These inhibitory effects of Necl-2 were mediated by the protein-tyrosine phosphatase PTPN13 which interacted with the cytoplasmic tail of Necl-2. We describe here this novel mechanism for silencing of the ErbB3/ErbB2 signaling by Necl-2.ErbB2 and ErbB3 are members of the EGF receptor/ErbB family, which has ErbB1 and ErbB4 as additional members (1). ErbB2 and ErbB3 are also known as HER2/Neu and HER3, respectively. No ligands binding directly to ErbB2 have been identified yet, whereas heregulin (HRG) 3 -␣ and -␤, also known as neuregulin-1 and -2, respectively, directly bind to ErbB3. ErbB2 and ErbB3 have kinase domains in their cytoplasmic tails, but that of ErbB3 lacks kinase activity. Therefore, the homodimer of ErbB3 formed by binding of HRG does not transduce any intracellular signaling. By contrast, ErbB2 heterophilically interacts in cis with HRG-occupied ErbB3 and phosphorylates nine tyrosine residues of ErbB3, causing recruitment and activation of the p85 subunit of phosphoinositide 3-kinase (PI3K) and the subsequent activation of Rac small G protein and Akt protein kinase (2). The activation of Rac enhances cell movement and that of Akt prevents cell apoptosis (3).ErbB2 serves as an oncogenic protein (4), and amplification of the ErbB2 gene is observed in many types of cancers. For instance, it is amplified in ϳ3% of lung cancers, ϳ30% of breast cancers, ϳ20% of gastric cancers, and ϳ60% of ovarian cancers (5). Moreover, mutation of the ErbB2 gene is found in many types of cancers, namely, ϳ10% of lung cancers, ϳ4% of breast cancers, ϳ5% of gastric cancers, and ϳ3% of colorectal cancers (6). This gene amplification or mutation causes enhanced signaling for cell movement and survival, eventually resulting in tumorigenesis, invasiveness, and metastasis. On the basis of these properties of ErbB2, it has been recognized as a good target for cancer therapy; indeed, ErbB2-targeting drugs have already been developed and used clinically (7,8). However, it remains unknown whether ErbB2 is involved in oncogenesis in cancers in which its gene is not amplified or mutated. In addition, it was recently reported that overexpression of ErbB3 is also involved in tumor malignancy (9), but it remains unknown how ErbB3 serves as an oncogenic p...

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“…In the context of a study exploring the therapeutic opportunity of targeting Fap-1 is expressed at high levels in several tumor types [36]; its implication in cancer is complex and context-dependent being reported as either a tumor promoting or a tumor suppressor in different studies [23,42,44]. Interestingly, the recent identification of Fap-1 as a target of the epithelial-to-mesenchymal transition regulator miR-200c, which is lost during cancer progression, provides a mechanistic explanation for the early loss of sensitivity of cancer cells to CD95-mediated apoptosis during neoplastic transformation [45].…”

Section: Discussionmentioning

confidence: 99%

Interplay between Ret and Fap-1 regulates CD95-mediated apoptosis in medullary thyroid cancer cells

Nicolini

Cassinelli

Cuccuru

et al. 2011

Biochemical Pharmacology

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Emerging evidence suggests that Ret oncoproteins expressed in medullary thyroid cancer (MTC) might evade the pro-apoptotic function of the dependence receptor proto-Ret by directly impacting the apoptosis machinery. Identification of the molecular determinants of the interplay between Ret signaling and apoptosis might provide a relevant contribution to the optimization of Ret-targeted therapies. Here, we describe the cross-talk between Ret-M918T oncogenic mutant responsible for type 2B multiple endocrine syndrome (MEN2B), and components of death receptor-mediated extrinsic apoptosis pathway. In the human MEN2B-type MTC cell line MZ-CRC-1 expressing Ret-M918T, Ret was found associated with Fap-1, known as inhibitor of the CD95 death receptor trafficking to the cell membrane, and with procaspase-8, the initiator pro-form caspase in the extrinsic apoptosis pathway. Cell treatment with the anti-tumor Ret kinase inhibitor RPI-1 inhibited tyrosine phosphorylation of procaspase-8, likely inducing its local activation, followed by downregulation of both Ret and

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PTPL1: a large phosphatase with a split personality

Cited by 54 publications

References 73 publications

miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer

miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer

Silencing of ErbB3/ErbB2 Signaling by Immunoglobulin-like Necl-2

Interplay between Ret and Fap-1 regulates CD95-mediated apoptosis in medullary thyroid cancer cells

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