Stomatin‐like protein 2 inhibits cisplatin‐induced apoptosis through MEK/ERK signaling and the mitochondrial apoptosis pathway in cervical cancer cells

• DOI: 10.1111/cas.13563
• Publication Date: 2018-03-08T08:16:38Z
• Authors: Guolin Hu; Jialu Zhang; Feifei Xu; Huan Deng; Weiwei Zhang; Shijun Kang; Weijiang Liang
• Keywords: Membrane Potential, Mitochondrial; 0303 health sciences; MAP Kinase Signaling System; Membrane Proteins; Uterine Cervical Neoplasms; Apoptosis; Original Articles; Blood Proteins; Mitochondria; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Drug Resistance, Neoplasm; Cell Line, Tumor; Humans; Calcium; Female; Cisplatin; Phosphorylation

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 Ca2+ 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.