LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells

Huang, Lijuan; Luan, Ting; Chen, Yujin; Bao, Xin; Huang, Yinglong; Shi, Fang; Wang, Haifeng; Wang, Jiansong

doi:10.7150/jca.23087

Cited by 19 publications

(15 citation statements)

References 34 publications

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“…Another study also elucidated the role of ERK-induced DRP1 phosphorylation in the chemoresistance of bladder cancer cells. The study reported that LASS2 inhibits bladder cancer invasion and chemoresistance through the regulation of ERK-DRP1-induced mitochondrial fission [ 90 ].…”

Section: Role Of Mitochondrial Remodeling (Fusion Fission Mitophagy and Transfer) In Cancer Chemoresistancementioning

confidence: 99%

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Genovese

Carinci

Modesti

et al. 2021

IJMS

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Mitochondria are key regulators of cell survival and are involved in a plethora of mechanisms, such as metabolism, Ca2+ signaling, reactive oxygen species (ROS) production, mitophagy and mitochondrial transfer, fusion, and fission (known as mitochondrial dynamics). The tuning of these processes in pathophysiological conditions is fundamental to the balance between cell death and survival. Indeed, ROS overproduction and mitochondrial Ca2+ overload are linked to the induction of apoptosis, while the impairment of mitochondrial dynamics and metabolism can have a double-faceted role in the decision between cell survival and death. Tumorigenesis involves an intricate series of cellular impairments not yet completely clarified, and a further level of complexity is added by the onset of apoptosis resistance mechanisms in cancer cells. In the majority of cases, cancer relapse or lack of responsiveness is related to the emergence of chemoresistance, which may be due to the cooperation of several cellular protection mechanisms, often mitochondria-related. With this review, we aim to critically report the current evidence on the relationship between mitochondria and cancer chemoresistance with a particular focus on the involvement of mitochondrial dynamics, mitochondrial Ca2+ signaling, oxidative stress, and metabolism to possibly identify new approaches or targets for overcoming cancer resistance.

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Section: Role Of Mitochondrial Remodeling (Fusion Fission Mitophagy and Transfer) In Cancer Chemoresistancementioning

confidence: 99%

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Genovese

Carinci

Modesti

et al. 2021

IJMS

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“…Previous studies demonstrated that activation of the AKT [ 71 , 72 , 73 ] and ERK [ 73 , 74 , 75 ] signaling is involved in mediating drug resistance and also linked to the upregulation of anti-apoptotic proteins such as XIAP [ 76 ]. We previously also found that paclitaxel-induced survivin expression is through activation of the PI3K-AKT and MEK-ERK1/2 pathways as the paclitaxel-resistant factor, and the inhibition of these two pathways by their specific inhibitors decreased survivin expression and sensitized paclitaxel efficacy in breast cancer cells [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Mutant Kras as a Biomarker Plays a Favorable Role in FL118-Induced Apoptosis, Reactive Oxygen Species (ROS) Production and Modulation of Survivin, Mcl-1 and XIAP in Human Bladder Cancer

Santha

Ling

Aljahdali

et al. 2020

Cancers

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Tumor heterogeneity in key gene mutations in bladder cancer (BC) is a major hurdle for the development of effective treatments. Using molecular, cellular, proteomics and animal models, we demonstrated that FL118, an innovative small molecule, is highly effective at killing T24 and UMUC3 high-grade BC cells, which have Hras and Kras mutations, respectively. In contrast, HT1376 BC cells with wild-type Ras are insensitive to FL118. This concept was further demonstrated in additional BC and colorectal cancer cells with mutant Kras versus those with wild-type Kras. FL118 strongly induced PARP cleavage (apoptosis hallmark) and inhibited survivin, XIAP and/or Mcl-1 in both T24 and UMUC3 cells, but not in the HT1376 cells. Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy. FL118 increased reactive oxygen species (ROS) production in T24 and UMUC3 cells, but not in HT1376 cells. Silencing mutant Kras in UMUC3 cells reduced FL118-mediated ROS generation. Proteomics analysis revealed that a profound and opposing Kras-relevant signaling protein is changed in UMUC3 cells and not in HT1376 cells. Consistently, in vivo studies indicated that UMUC3 tumors are highly sensitive to FL118 treatment, while HT1376 tumors are highly resistant to this agent. Silencing mutant Kras in UMUC3 cell-derived tumors decreases UMUC3 tumor sensitivity to FL118 treatment. Together, our studies revealed that mutant Kras is a favorable biomarker for FL118 targeted treatment.

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“…The effect of CerS-2 on BC invasion and chemoresistance is partly dependent on Drp1 signaling. CerS-2 can inhibit Drp1 signaling through regulation of ERK pathway [13]. Two genes closely related to cancer metastasis, called MMP-2 and MMP-9, had higher activities in BC cells knocked down for CerS-2 [12].…”

Section: Bladder Cancer (Bc)mentioning

confidence: 99%

Clinical and pathological significance ofHomo sapiensceramide synthase 2 (CerS-2) in diverse human cancers

et al. 2019

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Homo sapiens ceramide synthase 2 (CerS-2) plays an important role in inhibiting invasion and metastasis of tumor cells and has been reported as a tumor metastasis suppressor gene in diverse cancers. Thus, low level of CerS-2 protein might suggest a bad prognosis and up-regulation of CerS-2 protein might act as a promising therapeutic strategy for malignant tumors. In this review, we discussed the expression, as well as the clinical and pathological significance of CerS-2 in diverse human cancers. The pathological processes and molecular pathways regulated by CerS-2 were also summarized.

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LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells

Cited by 19 publications

References 34 publications

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Mutant Kras as a Biomarker Plays a Favorable Role in FL118-Induced Apoptosis, Reactive Oxygen Species (ROS) Production and Modulation of Survivin, Mcl-1 and XIAP in Human Bladder Cancer

Clinical and pathological significance ofHomo sapiensceramide synthase 2 (CerS-2) in diverse human cancers

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