TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer

Mohamad Elbaz, Dinesh Ahirwar, Zhang Xiaoli, Xinyu Zhou, Maryam Lustberg, Mohd W Nasser, Konstantin Shilo, Ramesh K. Ganju

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs. In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERa-) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy. In addition, we showed that TRPV2 overexpression or activation by CBD significantly increased doxorubicin (DOX) uptake and apoptosis in TNBC cells. The induction of DOX uptake was abrogated by TRPV2 blocking or downregulation. In vivo mouse model studies showed that the TNBC tumors derived from CBD+DOX treated mice have significantly reduced weight and increased apoptosis compared to those treated with CBD or DOX alone. Overall, our studies for the first time revealed that TRPV2 might be a good prognostic marker for TNBC and ERa-breast cancer patient especially for those who are treated with chemotherapy. In addition, TRPV2 activation could be a novel therapeutic strategy to enhance the uptake and efficacy of chemotherapy in TNBC patients.

Original languageEnglish (US)
Pages (from-to)33459-33470
Number of pages12
JournalOncotarget
Volume9
Issue number71
StatePublished - Sep 1 2018
Externally publishedYes

Fingerprint

Triple Negative Breast Neoplasms
TRPV Cation Channels
Biomarkers
Cannabidiol
Doxorubicin
Drug Therapy
Therapeutics
Estrogen Receptor alpha
Apoptosis
Breast Neoplasms
Ion Channels
Breast
Down-Regulation
Weights and Measures
Recurrence

Keywords

  • Chemotherapy
  • Doxorubicin
  • TNBC
  • TRPV2
  • Uptake

ASJC Scopus subject areas

  • Oncology

Cite this

Elbaz, M., Ahirwar, D., Xiaoli, Z., Zhou, X., Lustberg, M., Nasser, M. W., ... Ganju, R. K. (2018). TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer. Oncotarget, 9(71), 33459-33470.

TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer. / Elbaz, Mohamad; Ahirwar, Dinesh; Xiaoli, Zhang; Zhou, Xinyu; Lustberg, Maryam; Nasser, Mohd W; Shilo, Konstantin; Ganju, Ramesh K.

In: Oncotarget, Vol. 9, No. 71, 01.09.2018, p. 33459-33470.

Research output: Contribution to journalArticle

Elbaz, M, Ahirwar, D, Xiaoli, Z, Zhou, X, Lustberg, M, Nasser, MW, Shilo, K & Ganju, RK 2018, 'TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer', Oncotarget, vol. 9, no. 71, pp. 33459-33470.
Elbaz M, Ahirwar D, Xiaoli Z, Zhou X, Lustberg M, Nasser MW et al. TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer. Oncotarget. 2018 Sep 1;9(71):33459-33470.
Elbaz, Mohamad ; Ahirwar, Dinesh ; Xiaoli, Zhang ; Zhou, Xinyu ; Lustberg, Maryam ; Nasser, Mohd W ; Shilo, Konstantin ; Ganju, Ramesh K. / TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer. In: Oncotarget. 2018 ; Vol. 9, No. 71. pp. 33459-33470.
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