A novel frameshift mutation in TRPV6 is associated with hereditary pancreatitis

Shah, Ishfaq Ahmad; Prasad, Hari; Banerjee, Sumilan; Kurien, Reuben Thomas; Chowdhury, Sudipta Dhar; Visweswariah, Sandhya S.

doi:10.3389/fgene.2022.1058057

Cited by 2 publications

(1 citation statement)

References 54 publications

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“…These contradictory findings may reflect the heterogeneity and complexity of PDAC. Furthermore, it is known that TRPV6 impacts non-alcoholic early onset pancreatitis, a risk factor for the development of PDAC [17,18]. This was observed in several cohorts and appears to be correlated with the Ca 2+ channel activity of TRPV6 [19].…”

Section: Introductionmentioning

confidence: 93%

TRPV6 Channel Is Involved in Pancreatic Ductal Adenocarcinoma Aggressiveness and Resistance to Chemotherapeutics

Mesquita,

Haustrate,

Mihalache

et al. 2023

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) stands as a highly aggressive and lethal cancer, characterized by a grim prognosis and scarce treatment alternatives. Within this context, TRPV6, a calcium-permeable channel, emerges as a noteworthy candidate due to its overexpression in various cancers, capable of influencing the cell behavior in different cancer entities. Nonetheless, the exact expression pattern and functional significance of TRPV6 in the context of PDAC remains enigmatic. This study scrutinizes the expression of TRPV6 in tissue specimens obtained from 46 PDAC patients across distinct stages and grades. We manipulated TRPV6 expression (knockdown, overexpression) in the human PDAC cell lines Panc-1 and Capan-1. Subsequently, we analyzed its impact on multiple facets, encompassing Ca2+ influx, proliferation, apoptosis, migration, chemoresistance, and tumor growth, both in vitro and in vivo. Notably, the data indicate a direct correlation between TRPV6 expression levels, tumor stage, and grade, establishing a link between TRPV6 and PDAC proliferation in tissue samples. Decreasing TRPV6 expression via knockdown hampered Ca2+ influx, resulting in diminished proliferation and viability in both cell lines, and cell cycle progression in Panc-1. The knockdown simultaneously led to an increase in apoptotic rates and increased the susceptibility of cells to 5-FU and gemcitabine treatments. Moreover, it accelerated migration and promoted collective movement among Panc-1 cells. Conversely, TRPV6 overexpression yielded opposing outcomes in terms of proliferation in Panc-1 and Capan-1, and the migration of Panc-1 cells. Intriguingly, both TRPV6 knockdown and overexpression diminished the process of tumor formation in vivo. This intricate interplay suggests that PDAC aggressiveness relies on a fine-tuned TRPV6 expression, raising its profile as a putative therapeutic target.

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Section: Introductionmentioning

confidence: 93%

TRPV6 Channel Is Involved in Pancreatic Ductal Adenocarcinoma Aggressiveness and Resistance to Chemotherapeutics

Mesquita,

Haustrate,

Mihalache

et al. 2023

Cancers

View full text Add to dashboard Cite

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An integrated picture of chronic pancreatitis derived by mapping variants in multiple disease genes onto pathogenic pathways

Prasad,

Shah,

Kurien

et al. 2024

Human Molecular Genetics

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Chronic pancreatitis (CP) is an etiologically and genetically heterogeneous inflammatory syndrome characterised by progressive damage to the exocrine and endocrine components of the pancreas [ 1]. The multigenic paradigm of CP has sparked research in recent years [ 2]. We aimed to expand the current knowledge of genetic susceptibility of pancreatitis in patients of Indian origin. By employing whole-exome sequencing in an Indian hospital cohort, we dissect the genetic landscape associated with CP or recurrent acute pancreatitis (RAP). Notably, all patients had at least one genetic variant identified in a pancreatitis-risk gene, and most had a co-occurrence of a second variant in an additional risk gene. Based on the presence of both acinar and ductal gene variants in individual patients, we propose a two-hit hypothesis where variants in proteins expressed in both acinar and ductal cells are critical for RAP/CP development.

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A novel frameshift mutation in TRPV6 is associated with hereditary pancreatitis

Cited by 2 publications

References 54 publications

TRPV6 Channel Is Involved in Pancreatic Ductal Adenocarcinoma Aggressiveness and Resistance to Chemotherapeutics

TRPV6 Channel Is Involved in Pancreatic Ductal Adenocarcinoma Aggressiveness and Resistance to Chemotherapeutics

An integrated picture of chronic pancreatitis derived by mapping variants in multiple disease genes onto pathogenic pathways

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