Stomatin‐like protein 2 inhibits cisplatin‐induced apoptosis through MEK/ERK signaling and the mitochondrial apoptosis pathway in cervical cancer cells. Issue 5 (24th April 2018)

• Record Type: Journal Article
• Authors: Hu, Guolin; Zhang, Jialu; Xu, Feifei; Deng, Huan; Zhang, Weiwei; Kang, Shijun; Liang, Weijiang
• Is Part Of: Cancer science. Volume 109:Issue 5(2018)
• Page Start: 1357
• Page End: 1368
• Publication Date: 2018-04-24
• Subjects: cisplatin -- human cervical cancer -- MEK/ERK signaling -- mitochondrial apoptosis -- SLP‐2; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13563
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Stomatin‐like protein 2 (STOML2 or SLP‐2) is an oncogenic anti‐apoptotic protein that is upregulated in several types of cancer, including cervical cancer. However, the mechanisms responsible for the SLP‐2 anti‐apoptotic function remain poorly understood. Here, we show that siRNA‐mediated SLP‐2 suppression decreases growth of human cervical cancer HELA and SIHA cells, and increases cisplatin‐induced apoptosis through activation of MEK/ERK signaling and suppression of the mitochondrial pathway. The inhibition of the mitochondrial pathway is mediated by increasing the mitochondrial Ca 2+ concentration and mitochondrial membrane potential, thereby downregulating p‐MEK and p‐ERK levels, upregulating the Bax/Bcl‐2 ratio, increasing cytochrome C release from mitochondria into the cytosol, and upregulating levels of cleaved‐caspase 9, cleaved‐caspase 3, and cleaved poly ADP‐ribose polymerase (PARP). Overexpression of SLP‐2 using adenovirus‐STOML2 has the opposite effect: it upregulates p‐MEK and p‐ERK and downregulates the Bax/Bcl‐2 ratio and levels of cleaved‐caspase 9 to caspase 9, cleaved‐caspase 3 to caspase 3, and cleaved‐PARP to PARP in cisplatin‐treated cells. These data show that SLP‐2 inhibits cisplatin‐induced apoptosis by activating the MEK/ERK signaling and inhibiting the mitochondrial apoptosis pathway in cervical cancer cells. Abstract : SLP‐2 inhabits the apoptosis by the activation of MEK/ERK signaling pathway and the suppression of the mitochondrial apoptosis pathway in human cervical cancer cells and the expression of SLP‐2 is up‐regulated under stress of high cisplatin concentrations.