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Tumor Biology

, Volume 37, Issue 10, pp 13185–13203 | Cite as

Gene/protein expression of CAPN1/2-CAST system members is associated with ERK1/2 kinases activity as well as progression and clinical outcome in human laryngeal cancer

  • Katarzyna Starska
  • Ewa Forma
  • Paweł Jóźwiak
  • Iwona Lewy-Trenda
  • Marian Danilewicz
  • Olga Stasikowska-Kanicka
  • Michał Skóra
  • Katarzyna Kolary
  • Jakub Miazga
  • Anna Krześlak
  • Magdalena Bryś
Original Article

Abstract

Recent evidence indicates the involvement of calpains (CAPNs), a family of cysteine proteases, in cancer development and progression, as well as the insufficient response to cancer therapies. The contribution of CAPNs and regulatory calpastatin (CAST) and ERK1/2 kinases to aggressiveness, disease course, and outcome in laryngeal cancer remains elusive. This study was aimed to evaluate the CAPN1/2-CAST-ERK1/2 enzyme system mRNA/protein level and to investigate whether they can promote the dynamic of tumor growth and prognosis. The mRNA expression of marker genes was determined in 106 laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent mucosa (NCLM) controls using quantitative real-time PCR. The level of corresponding proteins was analyzed by Western Blot. SLUG expression, as indicator of pathological advancement was determined using IHC staining. Significant increases of CAPN1/2-CAST-ERK1/2 levels of mRNA/protein were noted in SCLC compared to NCLM (p < 0.05). As a result, a higher level of CAPN1 and ERK1 genes was related to larger tumor size, more aggressive and deeper growth according to TFG scale and SLUG level (p < 0.05). There were also relationships of CAPN1/2 and ERK1 with incidences of local/nodal recurrences (p < 0.05). An inverse association for CAPN1/2, CAST, and ERK1/2 transcripts was determined with regard to overall survival (p < 0.05). In addition, a higher CAPN1 and phospho-ERK1 protein level was related to higher grade and stage (p < 0.05) and was found to promote worse prognosis. This is the first study to show that activity of CAPN1/2- CAST-ERK1/2 axis may be an indicator of tumor phenotype and unfavorable outcome in SCLC.

Keywords

CAPN1 and CAPN2 genes CAST gene ERK1 and ERK2 genes Calpain-1 and calpain-2 proteins ERK1/2 kinases Calpastatin protein SLUG IHC expression Tumor front grading (TFG) Human laryngeal cancer 

Notes

Acknowledgments

This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811) and by a grant from the National Science Council, Poland (N403 043 32/2326).

Compliance with ethical standards

Conflicts of interest statement

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Katarzyna Starska
    • 1
  • Ewa Forma
    • 2
  • Paweł Jóźwiak
    • 2
  • Iwona Lewy-Trenda
    • 3
  • Marian Danilewicz
    • 3
  • Olga Stasikowska-Kanicka
    • 4
  • Michał Skóra
    • 5
  • Katarzyna Kolary
    • 6
  • Jakub Miazga
    • 6
  • Anna Krześlak
    • 2
  • Magdalena Bryś
    • 2
  1. 1.I Department of Otolaryngology and Laryngological OncologyMedical University of ŁódźLodzPoland
  2. 2.Department of CytobiochemistryUniversity of ŁódźLodzPoland
  3. 3.Department of PathologyMedical University of ŁódźLodzPoland
  4. 4.Department of NephropathologyMedical University of ŁódźLodzPoland
  5. 5.Department of OtolaryngologyŻeromski Specialist HospitalKrakowPoland
  6. 6.I Department of Otolaryngology and Laryngological Oncology, Student Scientific Circle of Laryngological, ImmunobiologyMedical University of ŁódźLodzPoland

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