<scp>CADM</scp>1 associates with Hippo pathway core kinases; membranous co–expression of <scp>CADM</scp>1 and <scp>LATS</scp>2 in lung tumors predicts good prognosis

Ito, Takeshi; Nakamura, Atsuko; Tanaka, Ichidai; Tsuboi, Yoshikatsu; Morikawa, Teppei; Nakajima, Jun; Takai, Daiya; Fukayama, Masashi; Sekido, Yoshitaka; Niki, Toshiro; Matsubara, Daisuke; Murakami, Yoshinori

doi:10.1111/cas.14040

Cited by 13 publications

(18 citation statements)

References 26 publications

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“…Moreover, RUXF and PGES2 are known to be involved in chemo-resistance in ovarian and colorectal cancer, respectively (18,19). On the other hand, CADM1 is shown to be a good prognostic marker in other cancers (20,21). Four proteins (i.e., TMED2, AGR2, JTB, and CADM1) among the over-expressed proteins in poor-responders ( Table 3) were predicted to be secreted extracellularly.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy

et al. 2020

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Background: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor-and good-NAC responders.Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good-and poor-NAC responders.Results: A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log 2 ratio > 2, p < 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients. Conclusion:A novel biomarker signature for poor-NAC response in PDAC was identified.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy

et al. 2020

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“…We previously showed that modest static pressure flattened epithelial cells and could inhibit their growth and slow the cell cycle through activation of YAP, a key transcriptional cofactor of the Hippo pathway [14]. In fact, CADM1 is shown to participate in the control of contact inhibition through the Hippo pathway in NIH3T3 fibroblastic cells and to form complexes with Hippo pathway core molecules LATS1, LATS2, MST1, and MST2 in HEK293 cells [30]. Clinically, co-expression of CADM1 and LATS2 on the cell membrane of cancer cells predicts good prognosis of lung adenocarcinoma [30].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, CADM1 is shown to participate in the control of contact inhibition through the Hippo pathway in NIH3T3 fibroblastic cells and to form complexes with Hippo pathway core molecules LATS1, LATS2, MST1, and MST2 in HEK293 cells [30]. Clinically, co-expression of CADM1 and LATS2 on the cell membrane of cancer cells predicts good prognosis of lung adenocarcinoma [30]. Collectively, CADM1 downregulation may promote apoptosis through involving the Hippo pathway based on the molecular interactions immediately beneath the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Cell Adhesion Molecule 1 Contributes to Cell Survival in Crowded Epithelial Monolayers

Hagiyama

Kimura

Yoneshige

et al. 2020

IJMS

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When epithelial cells in vivo are stimulated to proliferate, they crowd and often grow in height. These processes are likely to implicate dynamic interactions among lateral membranous proteins, such as cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member. Pulmonary epithelial cell lines that express CADM1, named NCI-H441 and RLE-6TN, were grown to become overconfluent in the polarized 2D culture system, and were examined for the expression of CADM1. Western analyses showed that the CADM1 expression levels increased gradually up to 3 times in a cell density-dependent manner. Confocal microscopic observations revealed dense immunostaining for CADM1 on the lateral membrane. In the overconfluent monolayers, CADM1 knockdown was achieved by two methods using CADM1-targeting siRNA and an anti-CADM1 neutralizing antibody. Antibody treatment experiments were also done on 6 other epithelial cell lines expressing CADM1. The CADM1 expression levels were reduced roughly by half, in association with cell height decrease by half in 3 lines. TUNEL assays revealed that the CADM1 knockdown increased the proportion of TUNEL-positive apoptotic cells approximately 10 folds. Increased expression of CADM1 appeared to contribute to cell survival in crowded epithelial monolayers.

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“…CADM1 (cell adhesion molecule‐1), also known as TSLC1, is expressed at the lateral membrane in normal epithelial cells 8,9 . CADM1 gene is a tumor suppressor and exerts a protect role in preventing malignant conversion and metastasis 10,11 .…”

Section: Introductionmentioning

confidence: 99%

“…CADM1 (cell adhesion molecule-1), also known as TSLC1, is expressed at the lateral membrane in normal epithelial cells. 8,9 CADM1 gene is a tumor suppressor and exerts a protect role in preventing malignant conversion and metastasis. 10,11 At present, more and more studies have demonstrated that CADM1 is related to cell proliferation, migration and invasion of various cancers, such as liver, 12 gastric 13 and breast cancers.…”

Section: Introductionmentioning

confidence: 99%

MiR‐423‐5p aggravates lung adenocarcinoma via targeting CADM1

Huang

Feng

2020

Thoracic Cancer

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Background: At present, microRNAs and its downstream genes have been regarded as influential indicators in various malignancies. Therefore, the aim of this study was to explore the relationship and molecular mechanism of the miR-423-5p and its downstream gene CADM1 in the LUAD. Methods: The pcDNA-CADM1 was used to construct the CADM1 overexpressed cell model. The cell proliferation was determined by CCK-8 and EdU assays and the cell metastasis was performed by wound scratch and transwell chamber assays. The relationship between miR-423-5p and CADM1 were determined by bioinformatics, luciferase reporter and western blot assays. Results: The results revealed that the CADM1 was downregulated in LUAD tissues and cell lines. CADM1 overexpression markedly repressed the cell proliferation, migration and invasion. Moreover, the results of bioinformatics, luciferase reporter and WB assays showed that CADM1 was a target gene of miR-423-5p and the miR-423-5p expression was negatively associated with CADM1 in LUAD cell lines. Finally, rescue experiments revealed that downregulation of CADM1 could antagonize the functions of miR-423-5p inhibitor on cell proliferation and metastasis. These results indicated that miR-423-5p aggravated lung adenocarcinoma via downregulation of CADM1 expression. Conclusions: Downregulation of CADM1 could antagonize the functions of miR-423-5p inhibitor on cell proliferation and metastasis. miR-423-5p aggravated lung adenocarcinoma via downregulation of CADM1 expression.

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CADM1 associates with Hippo pathway core kinases; membranous co–expression of CADM1 and LATS2 in lung tumors predicts good prognosis

Cited by 13 publications

References 26 publications

Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy

Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy

Cell Adhesion Molecule 1 Contributes to Cell Survival in Crowded Epithelial Monolayers

MiR‐423‐5p aggravates lung adenocarcinoma via targeting CADM1

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