HAX-1 overexpression, splicing and cellular localization in tumors

Trębińska, Alicja; Rembiszewska, Alina; Ciosek, Karolina; Ptaszyński, Konrad; Rowinski, Sebastian; Kupryjańczyk, Jolanta; Siedlecki, Janusz A.; Grzybowska, Ewa A.

doi:10.1186/1471-2407-10-76

Cited by 64 publications

(78 citation statements)

References 29 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Variants V-VIII are expressed at very low levels and contain frameshifts that change the protein sequence (Lees et al, 2008;Trebinska et al, 2010); therefore, only variants I-IV were analyzed in this study ( Fig. 2A, B).…”

Section: Hax-1-dcp1 Colocalization Is Hard To Disruptmentioning

confidence: 99%

HAX-1: A Novel P-Body Protein

Zayat¹,

Balcerak²,

Korczyński

et al. 2015

DNA and Cell Biology

Self Cite

View full text Add to dashboard Cite

HAX-1, a multifunctional protein involved in the regulation of apoptosis, cell migration, and calcium homeostasis, binds the 3¢ untranslated region motifs of specific transcripts. This suggests that HAX-1 plays a role in posttranscriptional regulation, at the level of mRNA stability/transport or translation. In this study, we analyze in detail HAX-1 colocalization with processing bodies (P-bodies) and its dependence on mRNA availability. Endogenous P-body markers DCP1 and Rck/p54 were shown to colocalize with endogenous HAX-1, but in case of the overexpressed proteins, only DCP1 displayed unperturbed colocalization with HAX-1. HAX-1 colocalization with DCP1 was observed in most of the cell lines studied, but its presence was not required for P-body formation, and its silencing caused an increase in P-body number. Preliminary mapping suggested that HAX-1 has more than one short P-body-targeting sequence. The pools of P-body-localized HAX-1 and cytosolic HAX-1 were demonstrated to dynamically exchange, suggesting steady flow of the protein. Active transcription was shown to be a factor in the localization of HAX-1 to P-bodies. Also, it was observed that HAX-1 localizes to some unidentified foci, which do not contain DCP1. In addition, it was demonstrated that HAX-1 status influences vimentin expression levels. Overall, HAX-1 was shown to colocalize with P-body markers and influence P-body number per cell in a manner dependent on mRNA availability. Presented data support the hypothesis that HAX-1 is involved in mRNA processing as an element of P-body interaction network.

show abstract

Section: Hax-1-dcp1 Colocalization Is Hard To Disruptmentioning

confidence: 99%

HAX-1: A Novel P-Body Protein

Zayat¹,

Balcerak²,

Korczyński

et al. 2015

DNA and Cell Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Patients with autosomal recessive forms of severe congenital neutropenia (SCN) or Kostmann disease, a condition associated with a maturation arrest in the bone marrow and a lack of mature neutrophils in peripheral blood, displayed mental retardation, attention deficit, epilepsy, and speech and gross motor retardation [13,17]. There is also emerging evidence that HAX-1 is overexpressed in various human premalignant epithelial dysplasic and oral squamous cell carcinomas [18] as well as in breast cancer tissues [19]. Therefore, the abnormally high levels of HAX-1 that are associated with cancer may be a consequence of HAX-1 0 s function as an anti-apoptotic protein.…”

Section: Introductionmentioning

confidence: 98%

Specific Alterations of the HtrA2/HAX-1 Ratio in the Penumbra Upon Focal Cerebral Ischemia in Mice

Rami

Langhagen

2011

Neurochem Res

View full text Add to dashboard Cite

HAX-1 is a mitochondrial protein which acts as an antiapoptotic protein in HeLa- and Jurkat cells after Fas-treatment, irradiation or serum deprivation. This underlines the evidence that HAX-1 might be involved in several apoptotic pathways. In this context, it is known that cell death executed by cerebral ischemia involves both receptor- and mitochondrial apoptotic mechanisms. In this study, we performed focal cerebral ischemia in mice and investigated principally the dynamic changes of HAX-1 expression and other apoptotic agents such as HtrA2, AIF and caspase-3. Western blot and immunohistochemistry analysis revealed that HAX-1 was expressed at very low levels under normal conditions. Focal cerebral ischemia significantly decreased cytosolic accumulation of HAX-1, induced an upregulation of HtrA2, an upregulation of AIF and activation of caspase-3. Taken together, these results suggested that HAX-1 is probably involved in the pathophysiology of cell death induced by focal ischemia.

show abstract

“…Studies indicate that variant II and variant III levels are reproducibly higher in tumors rather than normal tissues. 19 In addition, monoallelic loss of FBXO25 stabilizes HAX-1 in tumor cells. 26 Mechanisms were developed in tumor cells to overexpress the HAX-1.…”

Section: Discussionmentioning

confidence: 99%

“…17 In BC, previous studies have indicated that overexpression of HAX-1 promotes the development of cancers via improving their survival and is associated with the tumor size, stage, and grade of the disease. 18,19 The HAX-1 in cancers therefore has been reported as the new target for cancer therapy. 20 However, since the role of HAX-1 in BC treatment remains unclear, the aim of this study was thus to investigate the relationship between the chemoresistance and HAX-1 in BC.…”

Section: Introductionmentioning

confidence: 99%

Chemoresistance is associated with overexpression of HAX-1, inhibition of which resensitizes drug-resistant breast cancer cells to chemotherapy

Yang

Wang

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

Acquired resistance to standard chemotherapy is the common and critical limitation for cancer therapy. Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) has been reported to be upregulated in numerous cancers. However, the role of HAX-1 in oncotherapy remains unclear. In this study, we established MDA-MB-231 cell lines which were resistant to cisplatin (MDA-MB-231/CR) or doxorubicin (MDA-MB-231/DR) to study the chemoresistance in breast cancer. As a result, the HAX-1 which is an apoptosis-associated protein was observed to be overexpressed in both MDA-MB-231/CR and MDA-MB-231/DR compared with the routine MDA-MB-231 cells. Moreover, knockdown of HAX-1 via RNA interference decreased IC50 level of cisplatin by 70.91% in MDA-MB-231/CR cells, and the IC50 level of doxorubicin was decreased by 76.46% in MDA-MB-231/DR cells when the HAX-1 was downregulated. Additionally, we found that the knockdown of HAX-1 induced the release of cytochrome C from mitochondria, resulting in the activation of caspases. Taken together, our study indicates that the overexpression of HAX-1 is essential in the development of chemoresistance in breast cancer. Furthermore, we identify that HAX-1 may become the target for cancer therapy.

show abstract

HAX-1 overexpression, splicing and cellular localization in tumors

Cited by 64 publications

References 29 publications

HAX-1: A Novel P-Body Protein

HAX-1: A Novel P-Body Protein

Specific Alterations of the HtrA2/HAX-1 Ratio in the Penumbra Upon Focal Cerebral Ischemia in Mice

Chemoresistance is associated with overexpression of HAX-1, inhibition of which resensitizes drug-resistant breast cancer cells to chemotherapy

Contact Info

Product

Resources

About