Targeting Lymphangiogenesis and Lymph Node Metastasis in Liver Cancer

Roy, Sukanya; Banerjee, Priyanka; Ekser, Burçin; Bayless, Kayla J.; Zawieja, David C.; Alpini, Gianfranco; Glaser, Shannon; Chakraborty, Sanjukta

doi:10.1016/j.ajpath.2021.08.011

Cited by 28 publications

(32 citation statements)

References 97 publications

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“…Targeting lymphangiogenesis has been a challenge in recent years and there are currently no FDA-approved molecules that specifically inhibit lymphangiogenesis ( 21 ). Previous approaches — focused on lymphangiogenesis-pathway regulators, such as VEGF-C and VEGFR-3 — had mixed results for both the in vitro and in vivo models ( 22 ). Therefore, a possible combination of VEGF-C, KRAS and hnRNPA1 inhibitors could enhance an inhibitory effect on the tumor-induced lymphangiogenesis.…”

Section: Discussionmentioning

confidence: 99%

KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer

Pîrlog¹,

Calin²

2022

Journal of Clinical Investigation

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Kirsten rat sarcoma virus ( KRAS ) gene mutations are present in more than 90% of pancreatic ductal adenocarcinomas (PDACs). KRAS G12D is the most frequent alteration, promoting preneoplastic lesions and associating with a more aggressive phenotype. These tumors possess increased intratumoral lymphatic networks and frequent lymph node (LN) metastases. In this issue of the JCI , Luo, Li, et al. explored the relationship between the presence of the KRAS G12D mutation and lymphangiogenesis in PDAC. The authors used in vitro and in vivo models and an elegant mechanistic approach to describe an alternative pathway for lymphangiogenesis promotion. KRAS G12D induced SUMOylation of heterogenous nuclear ribonucleoprotein A1 (hnRNPA1) via SAE1 and SUMO2 activation. SUMOylated hnRNPA1 was loaded into extracellular vesicles (EVs) and internalized by human endothelial lymphatic cells (HLEC). Further, SUMOylated hnRNPA1 promoted lymphangiogenesis and LN metastasis by stabilizing prospero homeodomain protein 1 ( PROX1 ) mRNA. These data provide mechanistic insight into cancer lymphangiogenesis with the potential for developing biomarkers and RAS pathway therapeutics.

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Section: Discussionmentioning

confidence: 99%

KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer

Pîrlog¹,

Calin²

2022

Journal of Clinical Investigation

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“…Metastasis is a complicated process in which tumor cells migrate from their primary site and spread to other parts of the body to survive, adapt to conditions in a new tumor microenvironment, proliferate, and form new colonies at distant sites. The cellular and molecular interactions that occur in the tumor microenvironment greatly influence the migration and invasion potential of cancer cells [102][103][104]. In HCC, the process of metastasis is similarly complex as in other tumor types, and this complexity may complicate the prevention of tumor cell invasion.…”

Section: General Description Of Metastasis In Hccmentioning

confidence: 99%

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

et al. 2023

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Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Graphical abstract

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“…99 Tumour-associated lymphatic vessel density is closely correlated with sentinel lymph node metastasis, distant metastasis and patient survival. 100 In addition, lymph endothelial cells can interact with various immune cells to modulate immune cell activity. 101 By the above-mentioned means, lymphatic vessels can act as vital roles in the malignant progression of tumours.…”

Section: Exosomal Lncrnas and Lymphangiogenesis In Bcmentioning

confidence: 99%

The emerging roles of exosomal long non‐coding RNAs in bladder cancer

Liu

2022

J Cellular Molecular Medi

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Bladder cancer (BC) is one of the most common malignant tumours of the genitourinary system, accounting for the 9th most common malignant tumour in the world. 1,2 According to pathological classification, 90% of patients with BC have urothelial cancer. About one-third of these patients are first diagnosed with muscle invasive bladder cancer (MIBC). 3,4 In some patients, even if the first diagnosis is non-muscle invasive bladder cancer (NMIBC), 10%-30% of patients progress to MIBC. 4,5 BC has become a disease that seriously affects human health. 6,7 At present, its early diagnosis and treatment have made great progress, 8,9 but its specific mechanism of occurrence and development is still unclear.In recent years, non-coding RNAs (ncRNAs) have become a research hotspot. NcRNAs can be divided into housekeeping ncRNAs and regulatory ncRNAs. Among them, regulatory ncRNAs can be mainly divided into microRNA (miRNA), long noncoding RNA (ln-cRNA) and circular RNA (circRNA). [10][11][12][13] LncRNA is a general term for single-stranded nucleotide sequences exceeding 200 bp. 14 Although it does not have the function of encoding proteins, it can participate in gene regulation at the epigenetic level, transcription level and post-transcriptional level, 15-17 affect tumour occurrence, development, metastasis and malignant progression of drug resistance. [18][19][20][21][22][23] Based on the current research on the mechanism of lncRNA, the competitive endogenous 'ceRNA' mechanism is the most common type and a widely recognized regulatory mechanism, that is, some

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Targeting Lymphangiogenesis and Lymph Node Metastasis in Liver Cancer

Cited by 28 publications

References 97 publications

KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer

KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

The emerging roles of exosomal long non‐coding RNAs in bladder cancer

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