Targeting HGF/c-MET Axis in Pancreatic Cancer

Pothula, Srinivasa; Xu, Zhijian; Goldstein, David; Pirola, Romano C.; Wilson, Jeremy S.

doi:10.3390/ijms21239170

Cited by 48 publications

(40 citation statements)

References 110 publications

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“…CD82 can also regulate the distribution of proteins on the cell membrane by interacting with other molecules. When the protein undergoes palmitoylation modi cation, the protein located in the cytoplasm has the ability to anchor on the cell membrane, and the protein located on the cell membrane will promote the signal transport process and stably maintain normal physiological functions [3,14]. Palmitoylation contributes to the formation of the tetraspanin protein network and cell signal transduction [15,16].…”

Section: Discussionmentioning

confidence: 99%

“…When EGFR has not been activated, CD82 can down-regulate EGFR expression by regulating internalization kinetics. CD82 can also cooperate with vesicle-associated membrane protein and actin to change the signal transduction pathway of EGFR [2,3]. c-Met is also a receptor tyrosine kinase, which is mainly expressed in epithelial and endothelial cells [4].…”

Section: Introductionmentioning

confidence: 99%

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The Effects of CD82 Palmitoylation on the Metabolic Pathways of EGFR and c-Met in Breast Cancer Cells and their Molecular Mechanisms

Zhong

et al. 2021

Preprint

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Background: As a tumor metastasis suppressor, tetraspanin CD82 is reduced in many malignant tumors and often affects the composition of tumor microenvironment by changing the heterogeneity of cell membrane. EGFR or c-Met signaling pathway can regulate the metastasis ability of tumor cells and participate in the formation of tetraspanin web. The study of CD82 palmitoylation modification and metabolic pathway of tumor related molecules in tumor cells is still incomplete. This article focuses on studying the expression and distribution of EGFR and c-Met in cancer cells as well as related metabolic pathways and their molecular mechanisms after studying different palmitoylation site mutations.Methods: Western blot and immunofluorescence methods were used to detect the distribution of EGFR in breast cancer MDA-MB-231 cells after different CD82 palmitoylation site mutations. Then use the immunoprecipitation method to determine the interaction relationship between the molecules and the molecular mechanism.Results: We found that when CD82 combined with palmitoylation mutation at Cys5+Cys74 can enhance the internalization of EGFR, but has no effect on the expression and location of c-Met. When CD82 is combined with palmitoylation mutation at the Cys5+Cys74 site, with the assistance of tubulin, EGFR is internalized and strengthened by direct binding to CD82 and a large number of localizations on the recycling endosome. By forming the EGFR/CD82/Rab11a/FIP2 complex, it is metabolized through the circulation pathway, and re-expression of EGFR and CD82 on the cell membrane.Conclusions: From our results, we can demonatrate that CD82 palmitoylation mutation can change the distribution of EGFR in breast cancer cells, which may provide new ideas for breast cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effects of CD82 Palmitoylation on the Metabolic Pathways of EGFR and c-Met in Breast Cancer Cells and their Molecular Mechanisms

Zhong

et al. 2021

Preprint

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“…Together with its receptor, c-MET, HGF is overexpressed in PC and has been linked to cancer cell invasion, metastasis, and chemoresistance via tumor-promoting pathways such as P13/Akt and neuropilin (121)(122)(123)(124)(125). HGF levels predicted overall survival in locally advanced PC patients that underwent neoadjuvant therapy (126).…”

Section: Hepatocyte Growth Factor (Hgf)mentioning

confidence: 99%

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

et al. 2021

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Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

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“…And the expression of MACC1 is related to the degree of differentiation, depth of in ltration, lymph node metastasis and stage of gastric cancer [13] . Dysregulation of HGF/c-Met signaling has been reported as a prognostic marker for tumorigenesis, early invasion, and metastasis [14] . MACC1 may be highly expressed in esophageal squamous cell carcinoma, and its high expression may be associated with poor prognosis of esophageal carcinoma, but its speci c role and relationship remain to be explored.…”

Section: Introductionmentioning

confidence: 99%

The effect of SOX17, MACC1 and c-Met expression in ESCC on prognosis

Shi

et al. 2021

Preprint

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Aim: We mainly explored the expression of SOX17, MACC1 and c-Met in esophageal squamous cell carcinoma and their influence on the prognosis of patients.Methods：Expressions of SOX17, MACC1 and c-Met protein in a sample of 232 ESCC and adjacent nontumorous tissues were detected by immunohistochemistry. Their relationships and correlations with clinicopathological features and clinical prognosis were analyzed by SPSS 23.0.Results：SOX17 was associated with Vascular invasion (p=0.017) and Nerve invasion (p=0.014). MACC1 was correlated with Tumor size (p=0.039) and TNM stage (p=0.020).c-Met was significantly associated with hematogenous metastasis (p=0.045). The expression of MACC1 was correlated with c-Met (P<0.001). c-Met expression(p=0.021) were associated with OS. Conclusion: SOX17, MACC1 and c-Met may be new diagnostic targets for esophageal squamous cell carcinoma. c-Met may be a new therapeutic and prognostic target.

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Targeting HGF/c-MET Axis in Pancreatic Cancer

Cited by 48 publications

References 110 publications

The Effects of CD82 Palmitoylation on the Metabolic Pathways of EGFR and c-Met in Breast Cancer Cells and their Molecular Mechanisms

The Effects of CD82 Palmitoylation on the Metabolic Pathways of EGFR and c-Met in Breast Cancer Cells and their Molecular Mechanisms

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

The effect of SOX17, MACC1 and c-Met expression in ESCC on prognosis

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