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Kindlin?2 suppresses cervical cancer cell migration through AKT/mTOR?mediated autophagy induction.

ABSTRACT: Kindlin?2 plays a carcinogenic or tumor?suppressor role in various tumors. However, its role in cervical cancer remains unclear. In the present study, kindlin?2 expression was first analyzed using public expression data and clinical specimens. It was revealed that kindlin?2 was downregulated in cervical cancer tissues, and low expression of kindlin?2 was associated with poor disease?free survival. In addition, kindlin?2 was overexpressed and knocked down in two cell lines to study its effect in cervical cancer cells. The results revealed that kindlin?2 promoted cell autophagy and inactivated AKT/mTOR signaling. Rescue experiments indicated that the regulation of autophagy by kindlin?2 was dependent on the AKT/mTOR signaling pathway. Furthermore, it was revealed that kindlin?2 inhibited cell migration, and autophagy was required for this process. Collectively, these findings revealed the role and mechanism of kindlin?2 in the autophagy and migration of cervical cancer cells.

SUBMITTER: Wu G

PROVIDER: S-EPMC7251777 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Kindlin‑2 suppresses cervical cancer cell migration through AKT/mTOR‑mediated autophagy induction.

Wu Guangteng G Long Ying Y Lu Yan Y Feng Yiming Y Yang Xinmei X Xu Xun X Yao Desheng D

Oncology reports 20200504 1

Kindlin‑2 plays a carcinogenic or tumor‑suppressor role in various tumors. However, its role in cervical cancer remains unclear. In the present study, kindlin‑2 expression was first analyzed using public expression data and clinical specimens. It was revealed that kindlin‑2 was downregulated in cervical cancer tissues, and low expression of kindlin‑2 was associated with poor disease‑free survival. In addition, kindlin‑2 was overexpressed and knocked down in two cell lines to study its effect in ...[more]

PMID: 32377753

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Project description:α-Solanine is a glycoalkaloid found in species of the nightshade family including potato. It was primarily reported to have toxic effects in humans. However, there is a growing body of literature demonstrating in vitro and in vivo anticancer activity of α-solanine. Most of these studies have shown activation of apoptosis as the underlying mechanism in antitumor activity of α-solanine. In this study, we report α-solanine as a potential inducer of autophagy, which may act synergistically or in parallel with apoptosis to exert its cytotoxic effect. Induction of autophagy was demonstrated by several assays including electron microscopy, immunoblotting of autophagy markers and immunofluorescence for LC3 (microtubule-associated protein 1 (MAP1) light chain-3) puncta. α-Solanine-induced autophagic flux was demonstrated by additionally enhanced--turnover of LC3-II and--accumulation of LC3-specific puncta after co-incubation of cells with either of the autophagolysosome inhibitors--chloroquine and--bafilomycin A1. We also demonstrated α-solanine-induced oxidative damage in regulating autophagy where pre-incubation of cells with reactive oxygen species (ROS) scavenger resulted in suppression of CM-H2DCFDA (5 (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester) fluorescence as well as decrease in LC3-II turnover. α-Solanine treatment caused an increase in the expression of endoplasmic reticulum (ER) stress proteins (BiP, activating transcription factor 6 (ATF6), X-box-binding protein 1, PERK, inositol-requiring transmembrane kinase/endonuclease 1, ATF4 and CCAAT-enhancer-binding protein (C/EBP)-homologous protein) suggesting activation of unfolded protein response pathway. Moreover, we found downregulation of phosphorylated Akt (Thr308 and Ser473), mammalian target of rapamycin (mTOR; Ser2448 and Ser2481) and 4E-BP1 (Thr37/46) by α-solanine implying suppression of the Akt/mTOR pathway. Collectively, our results signify that α-solanine induces autophagy to exert anti-proliferative activity by triggering ER stress and inhibiting Akt/mTOR signaling pathway.

Dataset Information

Kindlin?2 suppresses cervical cancer cell migration through AKT/mTOR?mediated autophagy induction.

Publications

Kindlin‑2 suppresses cervical cancer cell migration through AKT/mTOR‑mediated autophagy induction.

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