Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2020

Open Access 01-12-2020 | Metastasis | Research

Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress

Authors: Weiwei Sheng, Guosen Wang, Jingtong Tang, Xiaoyang Shi, Rongxian Cao, Jian Sun, Yi Heng Lin, Chao Jia, Chuanping Chen, Jianping Zhou, Ming Dong

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

Login to get access

Abstract

Background

Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC.

Methods

We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo.

Results

Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients.

Conclusions

CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.
Appendix
Available only for authorised users
Literature
1.
2.
Fucikova J, Kasikova L, Truxova I, Laco J, Skapa P, Ryska A, et al. Relevance of the chaperone-like protein calreticulin for the biological behavior and clinical outcome of cancer. Immunol Lett. 2018;193:25–34.PubMedCrossRef
3.
Sheng W, Chen C, Dong M, Zhou J, Liu Q, Dong Q, et al. Overexpression of Calreticulin contributes to the development and progression of pancreatic Cancer. J Cell Physiol. 2014;229(7):887–97.PubMedCrossRef
4.
Sheng W, Chen C, Dong M, Wang G, Zhou J, Song H, et al. Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via integrin/EGFR-ERK/MAPK signaling pathway. Cell Death Dis. 2017;8(10):e3147.PubMedPubMedCentralCrossRef
5.
Limia CM, Sauzay C, Urra H, Hetz C, Chevet E, Avril T. Emerging Roles of the Endoplasmic Reticulum Associated Unfolded Protein Response in Cancer Cell Migration and Invasion. Cancers (Basel). 2019;11(5).
6.
Hsu SK, Chiu CC, Dahms HU, Chou CK, Cheng CM, Chang WT, et al. Unfolded protein response (UPR) in survival, dormancy, immunosuppression, metastasis, and treatments of Cancer cells. Int J Mol Sci. 2019;20(10):E2518.PubMedCrossRef
7.
Chen OI, Bobak YP, Stasyk OV, Kunz-Schughart LA. A complex scenario and underestimated challenge: the tumor microenvironment, ER stress, and Cancer treatment. Curr Med Chem. 2018;25(21):2465–502.PubMedCrossRef
8.
Kültz D. Molecular and evolutionary basis of the cellular stress response. Annu Rev Physiol. 2005;67:225–57.PubMedCrossRef
9.
Fulda S, Gorman AM, Hori O, Samali A. Cellular stress responses: cell survival and cell death. Int J Cell Biol. 2010;2010:214074.PubMedPubMedCentral
10.
Singh J, Hussain Y, Luqman S, Meena A. Targeting Ca2+ signalling through phytomolecules to combat cancer. Pharmacol Res. 2019;146:104282.PubMedCrossRef
11.
Bernales S, Soto MM, McCullagh E. Unfolded protein stress in the endoplasmic reticulum and mitochondria: a role in neurodegeneration. Front Aging Neurosci. 2012;4:5.PubMedPubMedCentralCrossRef
12.
Santoni G, Morelli MB, Marinelli O, Nabissi M, Santoni M, Amantini C. Calcium signaling and the regulation of Chemosensitivity in Cancer cells: role of the transient receptor potential channels. Adv Exp Med Biol. 2020;1131:505–17.PubMedCrossRef
13.
Dibdiakova K, Saksonova S, Pilchova I, Klacanova K, Tatarkova Z, Racay P. Both thapsigargin- and tunicamycin induced endoplasmic reticulum stress increases expression of Hrd1 in IRE1-dependent fashion. Neurol Res. 2019;41(2):177–88.PubMedCrossRef
14.
Wang G, Sheng W, Shi X, Li X, Zhou J, Dong M. Serine/arginine protein–specific kinase 2 promotes the development and progression of pancreatic cancer by downregulating numb and p53. FEBS J. 2019;286(9):1668–82.PubMedCrossRef
15.
Liu L, Wu N, Wang Y, Zhang X, Xia B, Tang J, et al. TRPM7 promotes the epithelial-mesenchymal transition in ovarian cancer through the calcium-related PI3K / AKT oncogenic signaling. J Exp Clin Cancer Res. 2019;38(1):106.PubMedPubMedCentralCrossRef
16.
Moon SY, Kim HS, Nho KW, Jang YJ, Lee SK. Endoplasmic reticulum stress induces epithelial-mesenchymal transition through autophagy via activation of c-Src kinase. Nephron Exp Nephrol. 2014;126(3):127–40.PubMedCrossRef
17.
Shin HS, Ryu ES, Oh ES, Kang DH. Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells. Lab Investig. 2015;95(10):1157–73.PubMedCrossRef
18.
Wu L, Huang X, Kuang Y, Xing Z, Deng X, Luo Z. Thapsigargin induces apoptosis in adrenocortical carcinoma by activatingendoplasmic reticulum stress and the JNK signaling pathway: an in vitro and in vivo study. Drug Des Devel Ther. 2019;13:2787–98.PubMedPubMedCentralCrossRef
19.
Lin Y, Jiang M, Chen W, Zhao T, Wei Y. Cancer and ER stress: mutual crosstalk between autophagy, oxidative stress and inflammatory response. Biomed Pharmacother. 2019;118:109249.PubMedCrossRef
20.
Ruiz A, Matute C, Alberdi E. Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes. Cell Death Dis. 2010;1:e54.PubMedPubMedCentralCrossRef
21.
Butler MR, Ma H, Yang F, Belcher J, Le YZ, Mikoshiba K, et al. Endoplasmic reticulum (ER) Ca2+−channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel deficiency. J Biol Chem. 2017;292(27):11189–205.PubMedPubMedCentralCrossRef
22.
Sheng X , Nenseth HZ, Qu S, Kuzu OF, Frahnow T, Simon L et al. IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling. Nat Commun 2019; 10(1):323.
23.
Auf G, Jabouille A, Guérit S, Pineau R, Delugin M, Bouchecareilh M, et al. Inositol-requiring enzyme 1α is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci U S A. 2010;107(35):15553–8.PubMedPubMedCentralCrossRef
24.
Li H, Chen X, Gao Y, Wu J, Zeng F, Song F. XBP1 induces snail expression to promote epithelial- to-mesenchymal transition and invasion of breast cancer cells. Cell Signal. 2015;27(1):82–9.PubMedCrossRef
25.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed
26.
Wang S, Huang S, Sun YL. Epithelial-Mesenchymal transition in pancreatic Cancer: a review. Biomed Res Int. 2017;2017:2646148.PubMedPubMedCentral
27.
Guarino M, Rubino B, Ballabio G. The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007;39(3):305–18.PubMedCrossRef
28.
Guarino M, Guarino M. Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol. 2007;39(12):2153–60.PubMedCrossRef
29.
Ostwald TJ, MacLennan DH. Isolation of a high affinity calcium binding protein from sarcoplasmic reticulum. J Biol Chem. 1974;249(3):974–9.PubMed
30.
31.
Venkateswaran K, Verma A, Bhatt AN, Shrivastava A, Manda K, Raj HG, et al. Emerging roles of Calreticulin in Cancer: implications for therapy. Curr Protein Pept Sci. 2018;19(4):344–57.PubMedCrossRef
32.
Zamanian M, Veerakumarasivam A, Abdullah S, Rosli R. Calreticulin and Cancer. Pathol Oncol Res. 2013;19:149–54.PubMedCrossRef
33.
Liu R, Gong J, Chen J, Li Q, Song C, Zhang J, et al. Calreticulin as a potential diagnostic biomarker for lung cancer. Cancer Immunol Immunother. 2012;61(6):855–64.PubMedCrossRef
34.
Zamanian M, Qader Hamadneh LA, Veerakumarasivam A, Abdul Rahman S, Shohaimi S, Rosli R. Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways. Cancer Cell Int. 2016;16:56.PubMedPubMedCentralCrossRef
35.
Lwin ZM, Guo C, Salim A, Yip GW, Chew FT, Nan J, et al. Clinicopathological significance of calreticulin in breast invasive ductal carcinoma. Mod Pathol. 2010;23(12):1559–66.PubMedCrossRef
36.
Chen CN, Chang CC, Su TE, Hsu WM, Jeng YM, Ho MC, et al. Identification of Calreticulin as a prognosis marker and Angiogenic regulator in human gastric Cancer. Ann Surg Oncol. 2009;16(2):524–33.PubMedCrossRef
37.
Yoon GS, Lee H, Jung Y, Yu E, Moon HB, Song K, et al. Nuclear matrix of calreticulin in hepatocellular carcinoma. Cancer Res. 2000;60(4):1117–20.PubMed
38.
Lu YC, Chen CN, Wang B, Hsu WM, Chen ST, Chang KJ, et al. Changes in tumor growth and metastatic capacities of J82 human bladder cancer cells suppressed by down-regulation of calreticulin expression. Am J Pathol. 2011;179(3):1425–33.PubMedPubMedCentralCrossRef
39.
Chiang WF, Hwang TZ, Hour TC, Wang LH, Chiu CC, Chen HR, et al. Calreticulin, an endoplasmic reticulum-resident protein, is highly expressed and essential for cell proliferation and migration in oral squamous cell carcinoma. Oral Oncol. 2013;49(6):534–41.PubMedCrossRef
40.
Du XL, Yang H, Liu SG, Luo ML, Hao JJ, Zhang Y, et al. Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3-CTTN-Akt pathway in esophageal squamous cell carcinoma. Oncogene. 2009;28(42):3714–22.PubMedCrossRef
41.
Shi F, Shang L, Pan BQ, Wang XM, Jiang YY, Hao JJ, et al. Calreticulin promotes migration and invasion of esophageal cancer cells by up-regulating neuropilin-1 expression via STAT5A. Clin Cancer Res. 2014;20(23):6153–62.PubMedCrossRef
42.
Hsu WM, Hsieh FJ, Jeng YM, Kuo ML, Chen CN, Lai DM, et al. Calreticulin expression in neuroblastoma-a novel independent prognostic factor. Ann Oncol. 2005;16(2):314–21.PubMedCrossRef
43.
Shih YY, Nakagawara A, Lee H, Juan HF, Jeng YM, Lin DT, et al. Calreticulin mediates nerve growth factor-induced neuronal differentiation. J Mol Neurosci. 2012;47(3):571–81.PubMedCrossRef
44.
Toquet C, Jarry A, Bou-Hanna C, Bach K, Denis MG, Mosnier JF, et al. Altered Calreticulin expression in human colon cancer: maintenance of Calreticulin expression is associated with mucinous differentiation. Oncol Rep. 2007;17(5):1101–7.PubMed
45.
Peng RQ, Chen YB, Ding Y, Zhang R, Zhang X, Yu XJ, et al. Expression of calreticulin is associated with infiltration of T-cells in stage IIIB colon cancer. World J Gastroenterol. 2010;16(19):2428–34.PubMedPubMedCentralCrossRef
46.
Vougas K, Gaitanarou E, Marinos E, Kittas C, Voloudakis-Baltatzis IE. Two-dimensional eleetrophoresis and immunohistochemical study of ealreticulin in colorectal adenocarcinoma and mirror biopsies. J BUON. 2008;13(1):101–7.PubMed
47.
Alfonso P, Núñez A, Madoz-Gurpide J, Lombardia L, Sánchez L, Casal JI. Proteomic expression analysis of colorectal cancer by two-dimensional differential gel electrophoresis. Proteomics. 2005;5(10):2602–11.PubMedCrossRef
48.
Alur M, Nguyen MM, Eggener SE, Jiang F, Dadras SS, Stern J, et al. Suppressive roles of calreticulin in prostate cancer growth and metastasis. Am J Pathol. 2009;175(2):882–90.PubMedPubMedCentralCrossRef
49.
Alaiya A, Roblick U, Egevad L, Carlsson A, Franzén B, Volz D, et al. Polypeptide expression in prostate hyperplasia and prostate adenocarcinoma. Anal Cell Pathol. 2000;21(1):1–9.PubMedPubMedCentralCrossRef
50.
Vaksman O, Davidson B, Tropé C, Reich R. Calreticulin expression is reduced in high-grade ovarian serous carcinoma effusions compared with primary tumors and solid metastases. Hum Pathol. 2013;44(12):2677–83.PubMedCrossRef
51.
Hellman K, Alaiya AA, Schedvins K, Steinberg W, Hellström AC, Auer G. Protein expression patterns in primary carcinoma of the vagina. Br J Cancer. 2004;91(2):319–26.PubMedPubMedCentralCrossRef
52.
53.
Bong AHL, Monteith GR. Calcium signaling and the therapeutic targeting of cancer cells. Biochim Biophys Acta, Mol Cell Res. 1865;2018:1786–94.
54.
55.
Davis FM, Azimi I, Faville RA, Peters AA, Jalink K, Putney JW Jr, et al. Induction of epithelial–mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent. Oncogene. 2014;33(18):2307–16.PubMedCrossRef
56.
57.
Bastianutto C, Clementi E, Codazzi F, Podini P, De Giorgi F, Rizzuto R, et al. Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. J Cell Biol. 1995;130(4):847–55.PubMedCrossRef
58.
Mery L, Mesaeli N, Michalak M, Opas M, Lew DP, Krause KH. Overexpression of calreticulin increases intracellular Ca2+ storage and decreases store-operated Ca2+ influx. J Biol Chem. 1996;271(16):9332–9.PubMedCrossRef
59.
Thastrup O, Cullen PJ, Drøbak BK, Hanley MR, Dawson AP. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990;87(7):2466–70.PubMedPubMedCentralCrossRef
60.
Hotz B, Arndt M, Dullat S, Bhargava S, Buhr HJ, Hotz HG. Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer. Clin Cancer Res. 2007;13(16):4769–76.PubMedCrossRef
61.
Assani G, Zhou Y. Effect of modulation of epithelial-Mesenchymal transition regulators Snail1 and Snail2 on Cancer cell Radiosensitivity by targeting of the cell cycle, cell apoptosis and cell migration/invasion. Oncol Lett. 2019;17(1):23–30.PubMed
62.
Navandar M, Garding A, Sahu SK, Pataskar A, Schick S, Tiwari VK. ERK Signalling modulates Epigenome to drive epithelial to Mesenchymal transition. Oncotarget. 2017;8(17):29269–81.PubMedPubMedCentralCrossRef
63.
Lu X, Law BK, Chytil AM, Brown KA, Aakre ME, Moses HL. Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia. 2004;6(5):603–10.CrossRef
64.
Sheng W, Shi X, Lin Y, Tang J, Jia C, Cao R, et al. Musashi2 promotes EGF-induced EMT in pancreatic Cancer via ZEB1-ERK/MAPK signaling. J Exp Clin Cancer Res. 2020;39(1):16.PubMedPubMedCentralCrossRef
65.
Chalmers F, Mogre S, Son J, Blazanin N, Glick AB. The multiple roles of the unfolded protein response regulator IRE1α in cancer. Mol Carcinog. 2019;58(9):1623–30.PubMedPubMedCentralCrossRef
66.
Wu Y, Shan B, Dai J, Xia Z, Cai J, Chen T, et al. Dual role for inositol-requiring enzyme 1α in promoting the development of hepatocellular carcinoma during diet-induced obesity in mice. Hepatology. 2018;68(2):533–46.PubMedCrossRef
67.
Zhang J, Liang Y, Lin Y, Liu Y, You Y, Yin W. IRE1α-TRAF2-ASK1 pathway is involved in CSTMP-induced apoptosis and ER stress in human non-small cell lung cancer A549 cells. Biomed Pharmacother. 2016;82:281–9.PubMedCrossRef
68.
Tang ZH, Su MX, Guo X, Jiang XM, Jia L, Chen X, et al. Increased expression of IRE1α associates with the resistant mechanism of Osimertinib (AZD9291)-resistant non-small cell lung Cancer HCC827/OSIR cells. Anti Cancer Agents Med Chem. 2018;18(4):550–5.CrossRef
69.
Li XX, Zhang HS, Xu YM, Zhang RJ, Chen Y, Fan L, et al. Knockdown of IRE1 inhibits colonic tumorigenesis through decreasing β-catenin and IRE1α targeting suppresses colon cancer cells. Oncogene. 2017;36(48):6738–46.PubMedCrossRef
70.
Xie Y, Liu C, Qin Y, Chen J, Fang J. Knockdown of IRE1ɑ suppresses metastatic potential of colon cancer cellsthrough inhibiting FN1-Src/FAK-GTPases signaling. Int J Biochem Cell Biol. 2019;114:105572.PubMedCrossRef
71.
Banerjee A, Ahmed H, Yang P, Czinn SJ, Blanchard TG. Endoplasmic reticulum stress and IRE-1 signaling cause apoptosis in colon cancer cells in response to andrographolide treatment. Oncotarget. 2016;7(27):41432–44.PubMedPubMedCentralCrossRef
72.
Chern YJ, Wong JCT, Cheng GSW, Yu A, Yin Y, Schaeffer DF, et al. The interaction between SPARC and GRP78 interferes with ER stress signalingand potentiates apoptosis via PERK/eIF2α and IRE1α/XBP-1 in colorectal cancer. Cell Death Dis. 2019;10(7):504.PubMedPubMedCentralCrossRef
73.
Wu R, Zhang Q-H, Lu Y-J, Ren K, Yi G-H. Involvement of the IRE1α-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases. DNA Cell Biol. 2015;34(1):6–18.PubMedPubMedCentralCrossRef
74.
Xie H, Tang C-HA, Song JH, Mancuso A, Del Valle JR, Cao J, et al. IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers. J Clin Invest. 2018;128(4):1300–16.PubMedPubMedCentralCrossRef
75.
Lin C, Li Q, She T, Li H, Yue Y, Gao S, et al. IRE1α-XBP1 signaling pathway, a potential therapeutic target in multiple myeloma. Leuk Res. 2016;49:7–12.CrossRef
76.
Huang H-W, Zeng X, Rhim T, Ron D, Ryoo HD. The requirement of IRE1 and XBP1 in resolving physiological stress during Drosophila development. J Cell Sci. 2017;130(18):3040–9.PubMedPubMedCentralCrossRef
77.
Ishikawa T, Kashima M, Nagano AJ, Ishikawa-Fujiwara T, Kamei Y, Todo T, et al. Unfolded Protein Response Transducer IRE1-mediated Signaling Independent of XBP1 mRNA Splicing Is Not Required for Growth and Development of Medaka Fish. Elife. 2017;6:e26845.PubMedPubMedCentralCrossRef
78.
Nguyên DT, Kebache S, Fazel A, Wong HN, Jenna S, Emadali A, et al. Nck-dependent activation of extracellular signal-regulated kinase-1 and regulation of cell survival during endoplasmic reticulum stress. Mol Biol Cell. 2004;15(9):4248–60.PubMedPubMedCentralCrossRef
79.
Zhang LJ, Chen S, Wu P, Hu CS, Thorne RF, Luo CM, et al. Inhibition of MEK blocks GRP78 up-regulation and enhances apoptosis induced by ER stress in gastric Cancer cells. Cancer Lett. 2009;274(1):40–6.PubMedCrossRef
Metadata
Title
Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress
Authors
Weiwei Sheng
Guosen Wang
Jingtong Tang
Xiaoyang Shi
Rongxian Cao
Jian Sun
Yi Heng Lin
Chao Jia
Chuanping Chen
Jianping Zhou
Ming Dong
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-020-01702-y

Other articles of this Issue 1/2020

Journal of Experimental & Clinical Cancer Research 1/2020 Go to the issue

Research

Transcription activation of circ-STAT3 induced by Gli2 promotes the progression of hepatoblastoma via acting as a sponge for miR-29a/b/c-3p to upregulate STAT3/Gli2

Research

The IL1β-IL1R signaling is involved in the stimulatory effects triggered by hypoxia in breast cancer cells and cancer-associated fibroblasts (CAFs)

Commentary

Reorganization of Istituti Fisioterapici Ospitalieri, an oncological and dermatological clinical and research center, to face the coronavirus health emergency: adopted measures and metrics of success to achieve and keep a COVID-19-free status

Research

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling

Research

LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway

Research

CircCDKN2B-AS1 interacts with IMP3 to stabilize hexokinase 2 mRNA and facilitate cervical squamous cell carcinoma aerobic glycolysis progression
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits